Incidence of three presentations of acute myocarditis in young men in military service. A 20-year experience.

PubMed

Karjalainen, J; Heikkilä, J

1999-08-01

The incidence of myocarditis is uncertain as diagnostic criteria have been vague. We evaluated the incidence of myocarditis presenting in three well defined forms (mimicking myocardial infarction, presenting as dilated cardiomyopathy, and as a cause of sudden death) in young men in military service over a 20-year period. The study population consisted of 672 672 Finnish men at a mean age of 20 years conscripted from 1977-1996. All those suspected of having myocardial disease were studied prospectively in the same institution. A clinical diagnosis of myocarditis mimicking myocardial infarction required ECG signs (ST-segment elevation followed by T-wave inversion) and a simultaneous detection of serum markers of acute myocardial injury (CK-MB and/or troponin T) in an infectious patient with chest pain. This form of myocarditis was diagnosed in 98 men, the incidence being 0.17 (95% CI 0.14-0.21). 1000 man-years(-1). Causative microbes were those commonly infecting the conscripts, but Coxsackievirus aetiology could be confirmed in only 4% of the cases. Nine patients presented with dilated cardiomyopathy of recent origin (incidence 0.02. 1000 man-years(-1)). None had histopathological evidence of myocarditis. Myocarditis caused one of the 10 sudden unexpected deaths (incidence 0.002. 1000 man-years(-1)). The usual presentation of acute myocarditis in young men mimicks alterations evoked by myocardial infarction but not those of dilated cardiomyopathy. Copyright 1999 The European Society of Cardiology.

Molecular screening by polymerase chain reaction detects panleukopenia virus DNA in formalin-fixed hearts from cats with idiopathic cardiomyopathy and myocarditis.

PubMed

Meurs, K M; Fox, P R; Magnon, A L; Liu, S; Towbin, J A

2000-01-01

Viral myocarditis has been suggested as an etiology for cardiomyopathy in several mammalian species. Myocarditis and idiopathic cardiomyopathy have been reported in the domestic cat, although a viral etiology has not been demonstrated. Because of the continuing interest in the potential relationship between viral myocarditis and cardiomyopathy, we evaluated hearts from cats with spontaneous, idiopathic cardiomyopathy for viral genomic material within myocytes by polymerase chain reaction, and for the presence of myocarditis by light microscopy. Thirty-one (31) formalin-fixed hearts from domestic cats who died of idiopathic cardiomyopathy were randomly selected from pathology archives. Seventeen (17) formalin-fixed hearts from healthy cats were similarly selected as normal controls. The polymerase chain reaction (PCR) was used to evaluate myocardial tissue for the presence of viral genome from feline panleukopenia virus, herpes virus, calici virus, and corona virus. Hearts were examined using light microscopy for histologic evidence of myocarditis according to the Dallas criteria. Panleukopenia virus was identified by PCR in 10 of 31 cats with cardiomyopathy but in none of the controls. Neither cardiomyopathic or control cats tested positive by PCR for herpes virus, calici virus, and corona virus. Myocarditis was detected by histologic examination in 18 of 31 cardiomyopathic cats and in none of 17 control cats. Myocarditis and or feline panleukopenia virus genome was detected in felines with idiopathic hypertrophic, dilated, and restrictive cardiomyopathy, suggesting a possible role of viral infection and inflammation in the pathogenesis of cardiomyopathy in this species.

Diagnostic approach of myocarditis: strike the golden mean.

PubMed

Hazebroek, M R; Everaerts, K; Heymans, S

2014-02-01

Myocarditis is a challenging diagnosis due to the extreme diversity of clinical manifestations. The actual incidence of myocarditis is also difficult to determine as endomyocardial biopsy (EMB), the diagnostic gold standard, is used infrequently. Nevertheless, in up to 30 % of patients with biopsy-proven myocarditis, progression to dilated cardiomyopathy (DCM) can occur and is associated with a poor prognosis. Recent position statements of the European Society of Cardiology (ESC) and the American Heart Association vary widely with regard to indications for performing an EMB in these patients. This makes decision-making, in particular for general practitioners (GPs) and regional hospitals, difficult and unclear. Therefore, we will present a short summary of the ESC Working Group on Myocardial and Pericardial Diseases statement and our suggestions for GPs and regional hospitals for the diagnostic approach in patients with suspected myocarditis.

Total artificial heart implantation for biventricular failure due to eosinophilic myocarditis.

PubMed

Kawabori, Masashi; Kurihara, Chitaru; Miller, Yair; Heck, Kent A; Bogaev, Roberta C; Civitello, Andrew B; Cohn, William E; Frazier, O H; Morgan, Jeffrey A

2017-09-01

Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

Update on Myocarditis and Inflammatory Cardiomyopathy: Reemergence of Endomyocardial Biopsy.

PubMed

Dominguez, Fernando; Kühl, Uwe; Pieske, Burkert; Garcia-Pavia, Pablo; Tschöpe, Carsten

2016-02-01

Myocarditis is defined as an inflammatory disease of the heart muscle and is an important cause of acute heart failure, sudden death, and dilated cardiomyopathy. Viruses account for most cases of myocarditis or inflammatory cardiomyopathy, which could induce an immune response causing inflammation even when the pathogen has been cleared. Other etiologic agents responsible for myocarditis include drugs, toxic substances, or autoimmune conditions. In the last few years, advances in noninvasive techniques such as cardiac magnetic resonance have been very useful in supporting diagnosis of myocarditis, but toxic, infectious-inflammatory, infiltrative, or autoimmune processes occur at a cellular level and only endomyocardial biopsy can establish the nature of the etiological agent. Furthermore, after the generalization of immunohistochemical and viral genome detection techniques, endomyocardial biopsy provides a definitive etiological diagnosis that can lead to specific treatments such as antiviral or immunosuppressive therapy. Endomyocardial biopsy is not commonly performed for the diagnosis of myocarditis due to safety reasons, but both right- and left endomyocardial biopsies have very low complication rates when performed by experienced operators. This document provides a state-of-the-art review of myocarditis and inflammatory cardiomyopathy, with special focus on the role of endomyocardial biopsy to establish specific treatments. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Macrophages and cardiac fibroblasts are the main producers of eotaxins and regulate eosinophil trafficking to the heart

PubMed Central

Diny, Nicola L.; Hou, Xuezhou; Barin, Jobert G.; Chen, Guobao; Talor, Monica V.; Schaub, Julie; Russell, Stuart D.; Klingel, Karin; Rose, Noel R.; Čiháková, Daniela

2016-01-01

Cardiac manifestations are a major cause of morbidity and mortality in patients with eosinophil-associated diseases. Eosinophils are thought to play a pathogenic role in myocarditis. We investigated the pathways that recruit eosinophils to the heart using a model of eosinophilic myocarditis, in which experimental autoimmune myocarditis (EAM) is induced in IFNγ−/−IL-17A−/− mice. Two conditions are necessary for efficient eosinophil trafficking to the heart: high eotaxin (CCL11, CCL24) expression in the heart and expression of the eotaxin receptor CCR3 by eosinophils. We identified cardiac fibroblasts as the source of CCL11 in the heart interstitium. CCL24 is produced by F4/80+ macrophages localized at inflammatory foci in the heart. Expression of CCL11 and CCL24 is controlled by Th2 cytokines, IL-4 and IL-13. To determine the relevance of this pathway in humans, we analyzed endomyocardial biopsy samples from myocarditis patients. Expression of CCL11 and CCL26 was significantly increased in eosinophilic myocarditis compared to chronic lymphocytic myocarditis and positively correlated with the number of eosinophils. Thus, eosinophil trafficking to the heart is dependent on the eotaxin-CCR3 pathway in a mouse model of EAM and associated with cardiac eotaxin expression in patients with eosinophilic myocarditis. Blocking this pathway may prevent eosinophil-mediated cardiac damage. PMID:27621211

Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

USDA-ARS?s Scientific Manuscript database

Myocarditis is often cited as the cause of fatalities associated with foot-and-mouth disease virus (FMDV) infection; however the pathogenesis of FMDV-associated myocarditis has not been described in detail. The current report describes substantial quantities of FMDV in association with a marked mono...

Phaeochromocytoma found on cardiovascular magnetic resonance in a patient presenting with acute myocarditis: an unusual association.

PubMed

Khattak, Sophia; Sim, Iain; Dancy, Luke; Whitelaw, Benjamin; Sado, Dan

2018-06-08

Myocarditis is inflammation of the cardiac muscle. The symptoms, signs and basic investigation findings can mimic that of myocardial infarction. The most common cause is infection (most commonly viral). Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive diagnostic test for potential acute myocarditis as it allows assessment of myocardial oedema and scar. A man aged 25 years was admitted with chest pain, dizziness, headache, palpitations and sweating. His troponin was mildly positive. A CMR was performed which showed mild myocarditis and a right suprarenal mass which was confirmed to be a phaeochromocytoma based on biochemistry and a dedicated imaging workup. Phaeochromocytoma can lead to cardiac involvement in the form of left ventricular dysfunction, or catecholamine-induced myocarditis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Myocarditis in auto-immune or auto-inflammatory diseases.

PubMed

Comarmond, Cloé; Cacoub, Patrice

2017-08-01

Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Myocarditis in athlete and myocardial bridge: An innocent bystander?

PubMed Central

Quaranta, Federico; Guerra, Emanuele; Sperandii, Fabio; De Santis, Francesco; Pigozzi, Fabio; Calò, Leonardo; Borrione, Paolo

2015-01-01

Myocarditis is a bacterial or viral inflammatory disease, often unnoticed or misdiagnosed. Athletes with myocarditis must stop practicing their activity since International medical Literature described some cases of sudden death. In the present report, we describe a case of an asymptomatic, apparently healthy, competitive athletes, who was diagnosed a myocarditis and as incidental finding a myocardial bridging. We focused the attention on the importance of anamnesis, electrocardiogram and athletes’ entourage for the diagnosis of such insidious pathologies and we evaluated the follow up, focusing the attention on electrocardiogram changes as well as on restitution ad integrum and prognosis, especially for the athletes. PMID:26015860

Parvovirus B19 is a bystander in adult myocarditis.

PubMed

Koepsell, Scott A; Anderson, Daniel R; Radio, Stanley J

2012-01-01

The genomic DNA of parvovirus B19, a small single-stranded DNA virus of the genus Erythrovirus, has been shown to persist in solid tissues of constitutionally healthy, immunocompetent individuals. Despite these data, many case reports and series have linked the presence of parvovirus B19 genomic DNA, detected through nucleic acid amplification testing, with myocarditis and cardiomyopathy. Herein, we use multiple tools to better assess the relationship between parvovirus B19 and myocarditis and cardiomyopathy. Nucleic acid amplification testing, immunohistochemistry, in situ hybridization, and electron microscopy were used to assess the location and activity of parvovirus B19 in cases of myocarditis and in cases with no significant cardiac disease. Nucleic acid amplification testing for parvovirus B19 genomic DNA was positive in 73% of patients with myocarditis/cardiomyopathy and in 26% of patients with no significant disease. In situ hybridization and immunohistochemistry showed that, in cases with amplifiable parvovirus B19 DNA, parvovirus B19 genomic DNA and viral protein production were present in rare mononuclear cells. In a majority of cases of myocarditis and a significant number of otherwise normal hearts, nucleic acid amplification testing detected persistent parvovirus B19 genomic DNA that did not play a significant pathogenic role. The source of parvovirus B19 DNA appeared to be interstitial mononuclear inflammatory cells and not myocardial or endothelial cells. Therefore, nucleic acid amplification testing alone is not diagnostically helpful for determining the etiology of adult myocarditis. Copyright © 2012 Elsevier Inc. All rights reserved.

Feasibility of FDG-PET in myocarditis: Comparison to CMR using integrated PET/MRI.

PubMed

Nensa, Felix; Kloth, Julia; Tezgah, Ercan; Poeppel, Thorsten D; Heusch, Philipp; Goebel, Juliane; Nassenstein, Kai; Schlosser, Thomas

2018-06-01

Besides cardiac sarcoidosis, FDG-PET is rarely used in the diagnosis of myocardial inflammation, while cardiac MRI (CMR) is the actual imaging reference for the workup of myocarditis. Using integrated PET/MRI in patients with suspected myocarditis, we prospectively compared FDG-PET to CMR and the feasibility of integrated FDG-PET/MRI in myocarditis. A total of 65 consecutive patients with suspected myocarditis were prospectively assessed using integrated cardiac FDG-PET/MRI. Studies comprised T2-weighted imaging, late gadolinium enhancement (LGE), and simultaneous PET acquisition. Physiological glucose uptake in the myocardium was suppressed using dietary preparation. FDG-PET/MRI was successful in 55 of 65 enrolled patients: two patients were excluded due to claustrophobia and eight patients due to failed inhibition of myocardial glucose uptake. Compared with CMR (LGE and/or T2), sensitivity and specificity of PET was 74% and 97%. Overall spatial agreement between PET and CMR was κ = 0.73. Spatial agreement between PET and T2 (κ = 0.75) was higher than agreement between PET and LGE (κ = 0.64) as well as between LGE and T2 (κ = 0.56). In patients with suspected myocarditis, FDG-PET is in good agreement with CMR findings.

Eosinophilic myocarditis due to Churg-Strauss syndrome with markedly elevated eosinophil cationic protein.

PubMed

Hara, Tomoya; Yamaguchi, Koji; Iwase, Takashi; Kadota, Muneyuki; Bando, Mika; Ogasawara, Kozue; Bando, Sachiko; Ise, Takayuki; Niki, Toshiyuki; Ueda, Yuka; Tomita, Noriko; Taketani, Yoshio; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka

2013-01-01

A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/μL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

Myocarditis in Patients With Antisynthetase Syndrome: Prevalence, Presentation, and Outcomes.

PubMed

Dieval, Céline; Deligny, Christophe; Meyer, Alain; Cluzel, Philippe; Champtiaux, Nicolas; Lefevre, Guillaume; Saadoun, David; Sibilia, Jean; Pellegrin, Jean-Luc; Hachulla, Eric; Benveniste, Olivier; Hervier, Baptiste

2015-07-01

Antisynthetase syndrome (aSS) corresponds to an overlapping inflammatory myopathy identified by various myositis-specific autoantibodies (directed against tRNA-synthetases). Myocardial involvement in this condition is poorly described.From a registry of 352 aSS patients, 12 cases of myocarditis were retrospectively identified on the basis of an unexplained increase in troponin T/I levels associated with either suggestive cardiac magnetic resonance imaging (MRI) findings, nonsignificant coronary artery abnormalities or positive endomyocardial biopsy.The prevalence of myocarditis in aSS is 3.4% and was not linked to any autoantibody specificity: anti-Jo1 (n = 8), anti-PL7 (n = 3), and anti-PL12 (n = 1). Myocarditis was a part of the first aSS manifestations in 42% of the cases and was asymptomatic (n = 2) or revealed by an acute (n = 4) or a subacute (n = 6) cardiac failure. It should be noted that myocarditis was always associated with an active myositis. When performed (n = 11), cardiac MRI revealed a late hypersignal in the T1-images in 73% of the cases (n = 8). Half of the patients required intensive care. Ten patients (83%) received dedicated cardiotropic drugs. Steroids and at least 1 immunosuppressive drug were given in all cases. After a median follow-up of 11 months (range 0-84) 9 (75%) patients recovered whereas 3 (25%) developed a chronic cardiac insufficiency. No patient died.The prevalence of myocarditis in aSS is similar to that of other inflammatory myopathies. Although the prognosis is relatively good, myocarditis is a severe condition and should be carefully considered as a possible manifestation in active aSS patients.

In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

PubMed Central

Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

2017-01-01

Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise localization of tissue damage free of MR contrast agents. PMID:28264039

ECG findings in comparison to cardiovascular MR imaging in viral myocarditis.

PubMed

Deluigi, Claudia C; Ong, Peter; Hill, Stephan; Wagner, Anja; Kispert, Eva; Klingel, Karin; Kandolf, Reinhard; Sechtem, Udo; Mahrholdt, Heiko

2013-04-30

We sought (1) to assess prevalence and type of ECG abnormalities in patients with biopsy proven myocarditis and signs of myocardial damage indicated by LGE, and (2) to evaluate whether ECG abnormalities are related to the pattern of myocardial damage. Prevalence and type of ECG abnormalities in patients presenting biopsy proven myocarditis, as well as any relation between ECG abnormalities and the in vivo pattern of myocardial damage are unknown. Eighty-four consecutive patients fulfilled the following criteria: (1) newly diagnosed biopsy proven viral myocarditis, and (2) non-ischemic LGE, and (3) standard 12-lead-ECG upon admission. Sixty-five patients with biopsy proven myocarditis had abnormal ECGs upon admission (77%). In this group, ST-abnormalities were detected most frequently (69%), followed by bundle-branch-block in 26%, and Q-waves in 8%. Atrial fibrillation was present in 6%, and AV-Block in two patients. In patients with septal LGE ST-abnormalities were more frequently located in anterolateral leads compared to patients with lateral LGE, in whom ST-abnormalities were most frequently observed in inferolateral leads. Bundle-branch-block occurred more often in patients with septal LGE (11/17). Four of five patients with Q-waves had severe and almost transmural LGE in the lateral wall. ECG abnormalities can be found in most patients with biopsy proven viral myocarditis at initial presentation. However, similar to suspected acute myocardial infarction, a normal ECG does not rule out myocarditis. ECG findings are related to the amount and area of damage as indicated by LGE, which confirms the important clinical role of ECG. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Toward evidence-based diagnosis of myocarditis in children and adolescents: Rationale, design, and first baseline data of MYKKE, a multicenter registry and study platform.

PubMed

Messroghli, Daniel R; Pickardt, Thomas; Fischer, Marcus; Opgen-Rhein, Bernd; Papakostas, Konstantin; Böcker, Dorothée; Jakob, André; Khalil, Markus; Mueller, Goetz C; Schmidt, Florian; Kaestner, Michael; Udink Ten Cate, Floris E A; Wagner, Robert; Ruf, Bettina; Kiski, Daniela; Wiegand, Gesa; Degener, Franziska; Bauer, Ulrike M M; Friede, Tim; Schubert, Stephan

2017-05-01

The aim of this registry is to provide data on age-related clinical features of suspected myocarditis and to create a study platform allowing for deriving diagnostic criteria and, at a later stage, testing therapeutic interventions in patients with myocarditis. After an initial 6-month pilot phase, MYKKE was opened in June 2014 as a prospective multicenter registry for patients from pediatric heart centers, university hospitals, and community hospitals with pediatric cardiology wards in Germany. Inclusion criteria consisted of age<18 years and hospitalization for suspected myocarditis as leading diagnosis at the discretion of the treating physician. By December 31, 2015, fifteen centers across Germany were actively participating and had enrolled 149 patients. Baseline data reveal 2 age peaks (<2 years, >12 years), show higher proportions of males, and document a high prevalence of severe disease courses in pediatric patients with suspected myocarditis. Severe clinical courses and early adverse events were more prevalent in younger patients and were related to severely impaired leftventricular ejection fraction at initial presentation. MYKKE represents a multicenter registry and research platform for children and adolescents with suspected myocarditis that achieve steady recruitment and generate a wide range of real-world data on clinical course, diagnostic workup, and treatment of this group of patients. The baseline data reveal the presence of 2 age peaks and provide important insights into the severity of disease in children with suspected myocarditis. In the future, MYKKE might facilitate interventional substudies by providing an established collaborating network using common diagnostic approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up.

PubMed

Berg, Jan; Kottwitz, Jan; Baltensperger, Nora; Kissel, Christine K; Lovrinovic, Marina; Mehra, Tarun; Scherff, Frank; Schmied, Christian; Templin, Christian; Lüscher, Thomas F; Heidecker, Bettina; Manka, Robert

2017-11-01

There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months. LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes. This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis. © 2017 American Heart Association, Inc.

Immune checkpoint inhibitor-related myocarditis.

PubMed

Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

2018-01-01

Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart. Evidence from studies using genetically engineered mouse models suggests that CTLA-4 signaling terminates proliferation and promotes anergy during the primary response to cardiac self-peptide recognition. PD-1 signaling restrains autoreactive T cells that enter the peripheral tissues and recognize cardiac-peptide, maintaining them in an anergic state. Patients affected by immune checkpoint inhibitor-related myocarditis often experience rapid onset of profound hemodynamic compromise progressing to cardiogenic shock. Early diagnosis is mandatory to address specific therapy and correct the timing of circulatory support. However, the diagnosis of myocarditis is challenging due to the heterogeneity of clinical presentations. Owing to its early onset, nonspecific symptomatology and fulminant progression, especially when these drugs are used in combination, oncologists should be vigilant for immune checkpoint inhibitor-related myocarditis. With many questions yet to be answered, from basic immune biology to clinical management, future research should aim to optimize the use of these drugs by identifying predictive biomarkers of either a response to therapy or the risks of myocarditis development. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies: an evaluation of their frequencies in deceased individuals with myocarditis and in non-inflamed control hearts.

PubMed

Nielsen, Trine Skov; Hansen, Jakob; Nielsen, Lars Peter; Baandrup, Ulrik Thorngren; Banner, Jytte

2014-09-01

Multiple viruses have been detected in cardiac tissue, but their role in causing myocarditis remains controversial. Viral diagnostics are increasingly used in forensic medicine, but the interpretation of the results can sometimes be challenging. In this study, we examined the prevalence of adenovirus, enterovirus, and parvovirus B19 (PVB) in myocardial autopsy samples from myocarditis related deaths and in non-inflamed control hearts in an effort to clarify their significance as the causes of myocarditis in a forensic material. We collected all autopsy cases diagnosed with myocarditis from 1992 to 2010. Eighty-four suicidal deaths with morphologically normal hearts served as controls. Polymerase chain reaction was used for the detection of the viral genomes (adenovirus, enterovirus, and PVB) in myocardial tissue specimens. The distinction between acute and persistent PVB infection was made by the serological determination of PVB-specific immunoglobulins M and G. PVB was detected in 33 of 112 (29 %) myocarditis cases and 37 of 84 (44 %) control cases. All of the samples were negative for the presence of adenovirus and enterovirus. Serological evidence of an acute PVB infection, determined by the presence of immunoglobulin M, was only present in one case. In the remaining cases, PVB was considered to be a bystander with no or limited association to myocardial inflammation. In this study, adenovirus, enterovirus, and PVB were found to be rare causes of myocarditis. The detection of PVB in myocardial autopsy samples most likely represents a persistent infection with no or limited association with myocardial inflammation. The forensic investigation of myocardial inflammation demands a thorough examination, including special attention to non-viral causes and requires a multidisciplinary approach.

IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis

PubMed Central

Grabie, Nir; Delfs, Michael W.; Westrich, Jason R.; Love, Victoria A.; Stavrakis, George; Ahmad, Ferhaan; Seidman, Christine E.; Seidman, Jonathan G.; Lichtman, Andrew H.

2003-01-01

Cardiac antigen–specific CD8+ T cells are involved in the autoimmune component of human myocarditis. Here, we studied the differentiation and migration of pathogenic CD8+ T cell effector cells in a new mouse model of autoimmune myocarditis. A transgenic mouse line was derived that expresses cardiac myocyte restricted membrane-bound ovalbumin (CMy-mOva). The endogenous adaptive immune system of CMy-mOva mice displays tolerance to ovalbumin. Adoptive transfer of naive CD8+ T cells from the ovalbumin-specific T cell receptor–transgenic (TCR-transgenic) OT-I strain induces myocarditis in CMy-mOva mice only after subsequent inoculation with ovalbumin-expressing vesicular stomatitis virus (VSV-Ova). OT-I effector T cells derived in vitro in the presence or absence of IL-12 were adoptively transferred into CMy-mOva mice, and the consequences were compared. Although IL-12 was not required for the generation of cytolytic and IFN-γ–producing effector T cells, only effectors primed in the presence of IL-12 infiltrated CMy-mOva hearts in significant numbers, causing lethal myocarditis. Furthermore, analysis of OT-I effectors collected from a mediastinal draining lymph node indicated that only effectors primed in vitro in the presence of IL-12 proliferated in vivo. These data demonstrate the importance of IL-12 in the differentiation of pathogenic CD8+ T cells that can cause myocarditis. PMID:12618521

[Familial spam (streptococcal pharyngitis associated myocarditis): is it a new entity or a coincidence?].

PubMed

Merav, Gil; Yassin, Aura; Rosenfeld, Inna; Hussein, Amer

2014-08-01

Myocarditis is an inflammation of the myocardium. It is potentially life-threatening, with a wide range of clinical presentations and most often it is caused by various viral, bacterial or fungal infections. A 27 year-old man, previously hospitalized due to streptococcal tonsillitis, was admitted to ED because of chest pain. He presented with pain, tightness irradiating to both shoulders and arms and associated sweating and vomiting. The ECG revealed ST elevations on Leads: V5-V6, V7-V9, II, III, AVF and ST depressions on Leads V1-V3. Laboratory results showed elevated Liver enzymes, and positive troponin-5.766 ng/mL The patient showed clinical improvement with NSAIDs and was diagnosed with myocarditis. His brother was admitted to the hospital a year earlier with a sore throat accompanied by chest pain and was diagnosed with perimyocarditis. The family history of myocarditis after a streptococcal infection, affecting two brothers a year apart from each other, raises the possibility that there is a genetic component responsible for an individuaLs susceptibility to develop myocarditis.

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).more » Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.« less

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

DOE PAGES

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; ...

2015-03-20

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).more » Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.« less

Predictors of the development of myocarditis or acute renal failure in patients with leptospirosis: An observational study

PubMed Central

2012-01-01

Background Leptospirosis has a varied clinical presentation with complications like myocarditis and acute renal failure. There are many predictors of severity and mortality including clinical and laboratory parameters. Early detection and treatment can reduce complications. Therefore recognizing the early predictors of the complications of leptospirosis is important in patient management. This study was aimed at determining the clinical and laboratory predictors of myocarditis or acute renal failure. Methods This was a prospective descriptive study carried out in the Teaching Hospital, Kandy, from 1st July 2007 to 31st July 2008. Patients with clinical features compatible with leptospirosis case definition were confirmed using the Microscopic Agglutination Test (MAT). Clinical features and laboratory measures done on admission were recorded. Patients were observed for the development of acute renal failure or myocarditis. Chi-square statistics, Fisher's exact test and Mann-Whitney U test were used to compare patients with and without complications. A logistic regression model was used to select final predictor variables. Results Sixty two confirmed leptospirosis patients were included in the study. Seven patients (11.3%) developed acute renal failure and five (8.1%) developed myocarditis while three (4.8%) had both acute renal failure and myocarditis. Conjunctival suffusion - 40 (64.5%), muscle tenderness - 28 (45.1%), oliguria - 20 (32.2%), jaundice - 12 (19.3%), hepatomegaly - 10 (16.1%), arrhythmias (irregular radial pulse) - 8 (12.9%), chest pain - 6 (9.7%), bleeding - 5 (8.1%), and shortness of breath (SOB) 4 (6.4%) were the common clinical features present among the patients. Out of these, only oliguria {odds ratio (OR) = 4.14 and 95% confidence interval (CI) 1.003-17.261}, jaundice (OR = 5.13 and 95% CI 1.149-28.003), and arrhythmias (OR = 5.774 and 95% CI 1.001-34.692), were predictors of myocarditis or acute renal failure and none of the laboratory measures could predict the two complications. Conclusions This study shows that out of clinical and laboratory variables, only oliguria, jaundice and arrhythmia are strong predictors of development of acute renal failure or myocarditis in patients with leptospirosis presented to Teaching Hospital of Kandy, Sri Lanka. PMID:22243770

A Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox and Influenza Vaccination

PubMed Central

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; Spooner, Christina; Hemann, Brian A.; Gibbs, Barnett T.; Atwood, J. Edwin; Howard, Robin S.; Chang, Audrey S.; Cruser, Daniel L.; Gates, Daniel G.; Vernalis, Marina N.; Lengkeek, Marguerite S.; McClenathan, Bruce M.; Jaffe, Allan S.; Cooper, Leslie T.; Black, Steve; Carlson, Christopher; Wilson, Christopher; Davis, Robert L.

2015-01-01

Background Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. Purpose The study’s primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. Methods New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. Conclusions Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized. PMID:25793705

Combined application of extracorporeal membrane oxygenation and an artificial pacemaker in fulminant myocarditis in a child

PubMed Central

Ye, Sheng; Zhu, Lvchan; Ning, Botao; Zhang, Chenmei

2017-01-01

Fulminant myocarditis is severe and aggressive, but it is self-limited and usually has a favorable prognosis if the patients can survive the acute phase. When drug treatment is not effective, extracorporeal membrane oxygenation technology should be applied to support cardiopulmonary function. Extracorporeal membrane oxygenation can simultaneously support function of the left ventricle, right ventricle, and lungs, and provide stable blood circulation for patients with heart and respiratory failure, which allows sufficient time for the cardiopulmonary system to recover. Fulminant myocarditis affects cardiac systolic function, as well as the function of autorhythmic cells and the conduction system. If severe bradycardia or atrioventricular block appears, a pacemaker needs to be installed. We report a child with fulminant myocarditis who was treated with extracorporeal membrane oxygenation combined with an artificial pacemaker. PMID:28747842

Combined application of extracorporeal membrane oxygenation and an artificial pacemaker in fulminant myocarditis in a child.

PubMed

Ye, Sheng; Zhu, Lvchan; Ning, Botao; Zhang, Chenmei

2017-06-01

Fulminant myocarditis is severe and aggressive, but it is self-limited and usually has a favorable prognosis if the patients can survive the acute phase. When drug treatment is not effective, extracorporeal membrane oxygenation technology should be applied to support cardiopulmonary function. Extracorporeal membrane oxygenation can simultaneously support function of the left ventricle, right ventricle, and lungs, and provide stable blood circulation for patients with heart and respiratory failure, which allows sufficient time for the cardiopulmonary system to recover. Fulminant myocarditis affects cardiac systolic function, as well as the function of autorhythmic cells and the conduction system. If severe bradycardia or atrioventricular block appears, a pacemaker needs to be installed. We report a child with fulminant myocarditis who was treated with extracorporeal membrane oxygenation combined with an artificial pacemaker.

Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis.

PubMed

Maxson, T R; Meurs, K M; Lehmkuhl, L B; Magnon, A L; Weisbrode, S E; Atkins, C E

2001-01-01

To perform polymerase chain reaction (PCR) analysis on paraffin-embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated. Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis. Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis. Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs.

Active myocarditis in a patient with chronic active Epstein-Barr virus infection.

PubMed

Takano, Hiroyuki; Nakagawa, Keiichi; Ishio, Naoki; Daimon, Michiko; Daimon, Masao; Kobayashi, Yoshio; Hiroshima, Kenzo; Komuro, Issei

2008-10-30

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by chronic or recurrent infectious mononucleosis-like symptoms and the prognosis of CAEBV infection is quite poor. The incidence of myocarditis as a complication of EBV infection is not so high and it is unusual that heart failure appears as the initial symptom. However, it is very important to detect and treat chronic active myocarditis in the early phase of CAEBV infection because chronic active myocarditis disorganizes and decreases cardiomyocytes, resulting in the progression to heart failure. We report a case of a 45-year-old man with CAEBV infection for 5 years. Echocardiography revealed moderate left ventricular systolic dysfunction with mild pericardial effusion. Endomyocardial biopsies demonstrated massive lymphocytic infiltration with adjacent myocytolysis and necrosis of cardiomyocytes suggesting active myocarditis. Immunohistological analysis of biopsies revealed that the infiltrating cells were mainly T lymphocytes. And some of the infiltrating cells showed a positive signal for the EBV-encoded small nuclear RNA by in situ hybridization. Positron emission tomography using (18)F-fluoro-2-deoxyglucose ((18)F-FDG) performed revealed increased uptake of (18)F-FDG of whole left ventricular wall with mild heterogeneity.

Myocarditis in children and detection of viruses in myocardial tissue: implications for immunosuppressive therapy.

PubMed

Camargo, Paulo Roberto; Okay, Thelma Suely; Yamamoto, Lídia; Del Negro, Gilda Maria Bárbaro; Lopes, Antonio Augusto

2011-04-14

There is scarce information on the potential benefits of immunosuppression in children with myocarditis and viral genomes in myocardium. We investigated the occurrence of myocarditis in children with a preliminary diagnosis of dilated cardiomyopathy, the frequency of cardiotropic viruses in the myocardium, and the response to immunosuppression. Thirty patients (nine months to 12 years) with left ventricular ejection fraction of 22.8 ± 4.1% were subjected to right cardiac catheterization and endomyocardial biopsy. Specimens were analyzed for the presence of inflammatory elements (Dallas criteria) and viral genome (polymerase chain reaction). Patients with active myocarditis received immunosuppressants (azatioprine and prednisone) and were re-catheterized nine months later. A historical control group of nine patients with myocarditis who did not receive immunosuppressants was included. Active myocarditis was diagnosed in ten patients (five with viral genomes detected). Immunosuppression resulted in a significant increase in left ventricular ejection fraction from 25.2 ± 2.8% to 45.7 ± 8.6% (versus 20.0 ± 4.0% to 22.0 ± 9.0% in historical controls, p<0.01) and cardiac index from 3.28 ± 0.51 L/min/m(2) to 4.40 ± 0.49 L/min/m(2) (versus 3.50 ± 0.40 L/min/m(2) to 3.70 ± 0.50 L/min/m(2) in controls, p<0.01), regardless of the presence of viral genomes (p=0.98 and p=0.22, respectively for the two variables). No relevant clinical events were observed. Non-inflammatory cardiomyopathy was diagnosed in 20 patients (seven with viral genomes). While on conventional therapy, there were four deaths and three assignments to transplantation, and no improvement of left ventricular ejection fraction in the remaining ones (22.5 ± 3.6% to 27.5 ± 10.6%). Children with chronic myocarditis seem to benefit from immunosuppressive therapy, regardless of the presence of viral genome in the myocardium. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Virus-Negative Active Lymphocytic Myocarditis Progressing to a Fibrotic Stage

PubMed Central

Gerbaud, Edouard; Vital, Anne; Erickson, Matthew; Montaudon, Michel; Harcaut, Emmanuel; Pellegrin, Jean luc; Laurent, François; Coste, Pierre

2011-01-01

We report a fairly special case of lymphocytic myocarditis progressing to a fibrotic stage, described using multimodality imaging and confirmed on histopathology. This paper presents an uncommon diagnosis with a probable guarded prognosis. PMID:21541190

Hitch-hiker taken for a ride: an unusual cause of myocarditis, septic shock and adult respiratory distress syndrome

PubMed Central

Kushawaha, Anurag; Brown, Mark; Martin, Ismael; Evenhuis, Walther

2013-01-01

Rocky Mountain spotted fever (RMSF) is a serious tick-borne illness caused by Rickettsia rickettsii that is endemic in southeastern USA. Although RMSF has been described as causing the classic clinical triad of fever, headache and a characteristic rash, serious and potentially life-threatening manifestations can occur. Cardiopulmonary involvement, although infrequent, may occur with severe cases of RMSF. Rickettsial myocarditis is an uncommon occurrence. We present a case of a previously healthy 26-year-old man, who was hitch-hiking across the southeastern USA, with serologically proven RMSF causing adult respiratory distress syndrome, septic shock and myocarditis manifested by elevated cardiac enzymes and decrease in myocardial function. After treatment with antibiotics, the myocarditis resolved. Therefore, although unusual, clinicians should be aware of possible myocardial involvement in patients with appropriate tick-exposure histories or other clinical signs of RMSF. PMID:23314875

A Case Report of Salmonella muenchen Enteritis Causing Rhabdomyolysis and Myocarditis in a Previously Healthy 26-Year-Old Man.

PubMed

Chapple, Will; Martell, Jon; Wilson, Joy S; Matsuura, Don T

2017-04-01

This case report examines an unusual presentation of a non-typhoidal Salmonella serovar with limited prevalence in the literature. This is the first case report to associate specifically the Salmonella muenchen serovar with rhabdomyolysis and myocarditis. This case report reviews the diagnostic criteria for myocarditis and explores the diagnostic dilemma of troponin elevation in the setting of rhabdomyolysis. It demonstrates that Salmonella muenchen has the ability to present in a broad range of individuals with complications extending beyond classical gastrointestinal symptoms. This report also concludes that diagnosis of the many possible complications from non-typhoidal Salmonella infections can be difficult due to patient comorbidities, variability in the severity of the illnesses, laboratory test limitations, and imaging limitations. When a patient presents with elevated troponins in the setting of rhabdomyolysis a careful workup should be done to evaluate for ischemic causes, myocarditis, or false elevation secondary to rhabdomyolysis.

Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

PubMed

Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Haskó, György; Čiháková, Daniela; Mechoulam, Raphael; Pacher, Pal

2016-01-08

Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors. Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T cell-infiltration, profound inflammatory response, fibrosis (measured by qRT-PCR, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.

Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

PubMed Central

Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Hask’, György; ’iháková, Daniela; Mechoulam, Raphael; Pacher, Pal

2016-01-01

Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell–mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell–mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation. PMID:26772776

Severe Enterovirus Infections in Hospitalized Children in the South of England: Clinical Phenotypes and Causative Genotypes.

PubMed

de Graaf, Hans; Pelosi, Emanuela; Cooper, Andrea; Pappachan, John; Sykes, Kim; MacIntosh, Iain; Gbesemete, Diane; Clark, Tristan W; Patel, Sanjay V; Faust, Saul N; Tebruegge, Marc

2016-07-01

Most enterovirus surveillance studies lack detailed clinical data, which limits their clinical usefulness. This study aimed to describe the clinical spectrum and outcome of severe enterovirus infections in children, and to determine whether there are associations between causative enterovirus genotypes and clinical phenotypes. Retrospective analysis of microbiological and clinical data from a tertiary children's hospital in the South of England over a 17-month period (2012-2013). In total, 30 patients were identified, comprising sepsis (n = 9), myocarditis (n = 8), meningitis (n = 8) and encephalitis (n = 5). Cases with sepsis or myocarditis were significantly younger than those with central nervous system disease (median age 21 and 15 days vs. 79 days; P = 0.0244 and P = 0.0310, respectively). There was considerable diversity in the causative genotypes in each of the clinical phenotypes, with some predominance of echoviruses in the meningitis group, and coxsackie B viruses in the myocarditis group. Thirteen cases required mechanical ventilation, 11 cases inotropic support, 3 cases dialysis and 3 cases extracorporal membrane oxygenation. The overall mortality was 10% (sepsis group, n = 1; myocarditis group, n = 2). Of the survivors, 5 (19%) had long-term sequelae (myocardial dysfunction, n = 2; neurological sequelae, n = 3). Patients with encephalitis had the longest hospital stay (median: 16 days), compared with 9, 6 and 3 days in patients with myocarditis, sepsis and meningitis, respectively (P = 0.005). Enterovirus infections, particularly enteroviral myocarditis and encephalitis, can cause significant morbidity and mortality. The results show that there are currently no strong associations between clinical phenotypes and particular causative enterovirus genotypes in the South of England.

The activating receptor NKG2D of natural killer cells promotes resistance against enterovirus-mediated inflammatory cardiomyopathy.

PubMed

Klingel, Karin; Fabritius, Cornelia; Sauter, Martina; Göldner, Katrin; Stauch, Diana; Kandolf, Reinhard; Ettischer, Nicole; Gahlen, Sabine; Schönberger, Tanja; Ebner, Susanne; Makrigiannis, Andrew P; Bélanger, Simon; Diefenbach, Andreas; Polić, Bojan; Pratschke, Johann; Kotsch, Katja

2014-10-01

In enterovirus-induced cardiomyopathy, information regarding the detailed impact of natural killer (NK) cells on the outcome of the disease is limited. We therefore hypothesized that NK cells and certain NK cell receptors determine the different outcome of coxsackievirus B3 (CVB3) myocarditis. Here, we demonstrate in murine models that resistance to chronic CVB3 myocarditis in immunocompetent C57BL/6 mice is characterized by significantly more mature CD11b(high) NK cells, the presence of NKG2D on NK cells, and enhanced NKG2D-dependent cytotoxicity compared to CVB3-susceptible A.BY/SnJ mice. The highly protective role of NKG2D in myocarditis was further proven by in vivo neutralization of NKG2D as well as in NKG2D-deficient mice but was shown to be independent of CD8(+) T-cell-dependent immunity. Moreover, the adoptive transfer of immunocompetent C57BL/6 NK cells pre- (day -1) as well as post-infectionem (day +2) displayed the potential to prevent permissive A.BY/SnJ mice from a progressive outcome of CVB3 myocarditis reflected by significantly improved cardiopathology and heart function. Altogether, our results provide firm evidence for a protective role of NKG2D-activated NK cells in CVB3 myocarditis leading to an effective virus clearance, thus offering novel therapeutic options in the treatment of virus-induced myocarditis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Lyme carditis with isolated left bundle branch block and myocarditis successfully treated with oral doxycycline.

PubMed

Cunha, Burke A; Elyasi, Maekal; Singh, Prince; Jimada, Ismail

2018-01-01

Lyme disease may present with a variety of cardiac manifestations ranging from first degree to third degree heart block. Cardiac involvement with Lyme disease may be asymptomatic, or symptomatic. Atrioventrical conduction abnormalities are the most common manifestation of Lyme carditis. Less common, are alternating right bundle branch block (RBBB) and left bundle branch block (LBBB). We present an interesting case of a young male whose main manifestation of Lyme carditis was isolated LBBB. He also had mild Lyme myocarditis. The patient was successfully treated with oral doxycycline, and his isolated LBBB and myocarditis rapidly resolved.

Recurrent lymphocytic myocarditis in a young male with ulcerative colitis

PubMed Central

2014-01-01

Awareness of myocarditis in association with inflammatory bowel diseases is crucial as it bears a rare but serious risk for mortality. This report describes the case of a young Caucasian male, whose heart biopsy was tested negative for giant cells and bacterial or viral genomes or proteins. He was experiencing severe lymphocytic myocarditis (other than mesalamine-induced) along with cardiogenic shock during ulcerative colitis exacerbation. This is an extremely rare, if not unique, clinical constellation. We chose to study the epidemiologic grounds and all major aspects of differential pathogenesis and treatment of this serious health problem. PMID:24576324

Heart failure caused by toxoplasmosis in a fennec fox (Fennecus zerda).

PubMed

Kottwitz, Jack J; Preziosi, Diane E; Miller, Margaret A; Ramos-Vara, Jose A; Maggs, David J; Bonagura, John D

2004-01-01

A male fennec fox (Fennecus zerda) kit was examined for lethargy, inappetence, and weight loss. Clinical findings included respiratory distress, a gallop rhythm, and retinochoroiditis. Radiography indicated pleural effusion and cardiomegaly. Echocardiographic findings included left ventricular dilatation, low left ventricular ejection fraction, and atrioventricular valvular regurgitation. Necropsy findings were compatible with a diagnosis of congestive heart failure caused by myocarditis. Histopathology showed a disseminated infection with Toxoplasma gondii causing myocarditis, skeletal polymyositis, gastrointestinal myositis, and panuveitis. Toxoplasma-induced myocarditis should be included in the differential diagnosis of heart failure and retinochoroiditis in the fennec fox.

Unexpected hazard of illegal immigration: Outbreak of viral myocarditis exacerbated by confinement and deprivation in a shipboard cargo container.

PubMed

Li, Melissa K; Beck, Melinda A; Shi, Qing; Harruff, Richard C

2004-06-01

We present a group of 18 illegal immigrant stowaways who arrived in a shipboard cargo container suffering from gastroenteritis, dehydration, and malnutrition and showing evidence of viral myocarditis in 3 of 4 fatalities. Our investigation included an evaluation of the 2-week ocean voyage, analysis of medical records and laboratory results of the survivors, autopsies on the decedents, and viral studies on their heart tissue. Of 3 stowaways who died shipboard, 2 showed lymphocytic myocarditis and 1 could not be evaluated histologically due to decomposition. A fourth stowaway died 4 months after arrival with dilated cardiomyopathy and lymphocytic myocarditis. Reverse-transcriptase polymerase chain reaction and nucleotide sequencing of viral isolates from the decedents' heart tissues demonstrated Coxsackie virus B3 genome. We believe that these cases represent an outbreak of viral myocarditis, exacerbated by acute dehydration and malnutrition, due to confinement within the shipping container. Our evidence indicates that close confinement promoted the spread of the virus, and nutritional deprivation increased the stowaways' vulnerability. Furthermore, our observations support the conclusion, based on experimental studies, that nutritionally induced oxidative stress increased the virulence of the etiologic viral agent. In summary, these cases represent a potential infectious disease hazard of illegal immigration.

[Effect of immune therapy in the prognosis of viral myocarditis in pediatric patients].

PubMed

Márquez-González, Horacio; López-Gallegos, Diana; González-Espinosa, Alicia María Dolores; Zamudio-López, Jonathan Omar; Yáñez-Gutiérrez, Lucelli

2016-01-01

Myocarditis is the inflammation of the myocardial tissue, primarily caused by viral infection. Dilated cardiomyopathy (MD) is the most serious complication. Immunomodulatory therapy is not validated in these patients; however, it appears to offer benefits in the prognosis of this disease. The aim of this work was to determine the prognosis of immunomodulatory therapy in the development of MD in pediatric patients with viral myocarditis effect. A retrospective cohort of patients between 4 and 17 years diagnosed with viral myocarditis was integrated. It was considered as the main exposure treatment, which was divided into two types: normal (drugs targeted for heart failure and antiviral exclusively) and immunomodulatory (hyperimmune immunoglobulin, azathioprine and prednisone plus usual treatment). Time between diagnosis and treatment, history of asystole and positive for enterovirus and adenovirus antibodies: as measured confounders. The follow-up was 48 months. The outcome variable was the MD (LV diastolic diameter > + 2 Z-score and positive biopsy). 31 patients were obtained with a median of 5 (4-15) years; 6 received immunomodulatory therapy and regular rest. The MD was presented in 17% of patients exposed to immunomodulatory therapy vs. 35% traditional, with HR = 0.5 (0.1-0.7). Inmunodulatory therapy is a protective factor for MD in patients with viral myocarditis.

Sudden unexpected death related to enterovirus myocarditis: histopathology, immunohistochemistry and molecular pathology diagnosis at post-mortem

PubMed Central

2012-01-01

Background Viral myocarditis is a major cause of sudden unexpected death in children and young adults. Until recently, coxsackievirus B3 (CVB3) has been the most commonly implicated virus in myocarditis. At present, no standard diagnosis is generally accepted due to the insensitivity of traditional diagnostic tests. This has prompted health professionals to seek new diagnostic approaches, which resulted in the emergence of new molecular pathological tests and a more detailed immunohistochemical and histopathological analysis. When supplemented with immunohistochemistry and molecular pathology, conventional histopathology may provide important clues regarding myocarditis underlying etiology. Methods This study is based on post-mortem samples from sudden unexpected death victims and controls who were investigated prospectively. Immunohistochemical investigations for the detection of the enteroviral capsid protein VP1 and the characterization and quantification of myocardial inflammatory reactions as well as molecular pathological methods for enteroviral genome detection were performed. Results Overall, 48 sudden unexpected death victims were enrolled. As for controls, 37 cases of unnatural traffic accident victims were studied. Enterovirus was detected in 6 sudden unexpected death cases (12.5 %). The control samples were completely enterovirus negative. Furthermore, the enteroviral capsid protein VP1 in the myocardium was detected in enterovirus-positive cases revealed by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Unlike control samples, immunohistochemical investigations showed a significant presence of T and B lymphocytes in sudden unexpected death victims. Conclusions Our findings demonstrate clearly a higher prevalence of viral myocarditis in cases of sudden unexpected death compared to control subjects, suggesting that coxsackie B enterovirus may contribute to myocarditis pathogenesis significantly. PMID:22966951

Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs.

PubMed

Ford, Jordan; McEndaffer, Laura; Renshaw, Randall; Molesan, Alex; Kelly, Kathleen

2017-11-01

Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%-45%) and 2 of 41 controls (5%; 95% CI, 0.1%-16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.

Trypanosoma cruzi persistence in the native heart is associated with high-grade myocarditis, but not with Chagas' disease reactivation after heart transplantation.

PubMed

Benvenuti, Luiz A; Roggério, Alessandra; Nishiya, Anna S; Campos, Silvia V; Fiorelli, Alfredo I; Levi, José E

2014-07-01

Chagas' disease reactivation (CDR) after heart transplantation (HTx) is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. We investigated whether a detailed pathologic examination of the explanted heart at HTx with evaluation of myocarditis and parasitic persistence or load in the myocardium could be useful to identify patients at high risk of CDR. The native hearts of 18 chagasic patients who presented CDR after HTx (CDR+ group) were compared with the native hearts of 16 chagasic patients who never presented CDR in a follow-up of at least 18 months after HTx (CDR- group). The intensity of myocarditis was evaluated semiquantitatively. Parasite persistence/load in the myocardium was investigated through immunohistochemistry for T cruzi antigens and by qualitative and quantitative real-time PCR for T cruzi DNA. The rate of high-grade myocarditis, parasite persistence, and the median of parasitic load and parasitic load/10(6) cells in the CDR+ group were 83.3%, 77.8%, 8.43 × 10(-3), and 9.890, respectively, whereas in the CDR- group the values were 87.5%, 50%, 7.49×10(-3), and 17.800. There was no statistical difference between the groups. High-grade myocarditis was present in all 22 samples (100%) with parasite persistence and in 7 of 12 samples (58.3%) with no parasite persistence (p = 0.003). Although associated with high-grade myocarditis, T cruzi parasite persistence in the myocardium of the native heart is not associated with the occurrence of CDR after HTx. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

[Diagnostic value of cardiac magnetic resonance in patients with acute viral myocarditis].

PubMed

Ouyang, Haichun; Chen, Haixiong; Hu, Yunzhao; Wu, Yanxian; Li, Wensheng; Chen, Yuying; Cen, Yujian

2014-11-01

To assess the diagnostic value of cardiac magnetic resonance (CMR) in patients with acute viral myocarditis. Thirty patients with suspected acute viral myocarditis admitted in first people's hospital of Shunde from June 2011 to June 2013 were included in this prospective study. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of acute viral myocarditis were evaluated by clinical diagnosis. Diagnostic value among different scan methods and Lake Louise criteria were compared. Acute viral myocarditis was diagnosed in 63.33% (19/30) patients.Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall cohort were 57.89%, 72.73%, 78.57%, 50.00%, 63.33%, respectively by edema imaging (ER).Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall cohort were 78.95%, 63.64%, 78.95%, 63.64%, 73.33%, respectively using global relative enhancement (gRE).Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall cohort were 78.95%, 54.55%, 75.00%, 60.00%, 70.00%, respectively using late gadolinium enhancement (LGE) criteria.Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall cohort were 84.21%, 81.82%, 88.89%, 75.00%, 83.33% using Lake Louise criteria. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy using Lake Louise criteria were significantly higher than using ER, gRE, LGE alone(all P < 0.05).Specificity was higher using ER than using gRE and LGE (both P < 0.05). The sensitivity, NPV, and diagnostic accuracy were significantly higher using gRE than using ER (all P < 0.05) and was similar as using LGE (all P > 0.05). Cardiac magnetic resonance is an excellent imaging modality for the diagnosis of acute viral myocarditis.

Severe Enterovirus Infections in Hospitalized Children in the South of England

PubMed Central

de Graaf, Hans; Pelosi, Emanuela; Cooper, Andrea; Pappachan, John; Sykes, Kim; MacIntosh, Iain; Gbesemete, Diane; Clark, Tristan W.; Patel, Sanjay V.; Faust, Saul N.

2016-01-01

Background: Most enterovirus surveillance studies lack detailed clinical data, which limits their clinical usefulness. This study aimed to describe the clinical spectrum and outcome of severe enterovirus infections in children, and to determine whether there are associations between causative enterovirus genotypes and clinical phenotypes. Methods: Retrospective analysis of microbiological and clinical data from a tertiary children’s hospital in the South of England over a 17-month period (2012–2013). Results: In total, 30 patients were identified, comprising sepsis (n = 9), myocarditis (n = 8), meningitis (n = 8) and encephalitis (n = 5). Cases with sepsis or myocarditis were significantly younger than those with central nervous system disease (median age 21 and 15 days vs. 79 days; P = 0.0244 and P = 0.0310, respectively). There was considerable diversity in the causative genotypes in each of the clinical phenotypes, with some predominance of echoviruses in the meningitis group, and coxsackie B viruses in the myocarditis group. Thirteen cases required mechanical ventilation, 11 cases inotropic support, 3 cases dialysis and 3 cases extracorporal membrane oxygenation. The overall mortality was 10% (sepsis group, n = 1; myocarditis group, n = 2). Of the survivors, 5 (19%) had long-term sequelae (myocardial dysfunction, n = 2; neurological sequelae, n = 3). Patients with encephalitis had the longest hospital stay (median: 16 days), compared with 9, 6 and 3 days in patients with myocarditis, sepsis and meningitis, respectively (P = 0.005). Conclusions: Enterovirus infections, particularly enteroviral myocarditis and encephalitis, can cause significant morbidity and mortality. The results show that there are currently no strong associations between clinical phenotypes and particular causative enterovirus genotypes in the South of England. PMID:26882165

[Cardiac tamponade and myocarditis in Churg-Strauss syndrome].

PubMed

Baili, L; Aydi, Z; Soussi, G; Ben Dhaou B, B; Zidi, A; Berraies, A; Boussema, F; Kammoun, S; Hamzaoui, A; Kraiem, S; Ben Miled M'rad, K; Rokbani, L

2014-09-01

The successive occurrence of pericardial tamponade and myocarditis during a Churg-Strauss syndrome is exceptionally described. We report a patient in whom pericardial tamponade and myocarditis were the presenting manifestation of a Churg-Strauss syndrome. A 58-year-old woman was admitted because of alteration of the clinical status with eosinophilia. One month ago, she was hospitalized for a pericardial tamponade treated by pericardial drainage. Acute myocarditis was diagnosed on chest pain during the second hospitalization. The etiologic inquiry ended in the diagnosis of Churg-Strauss complicated with a double cardiac involvement. A good response of clinical and biological anomalies was obtained after corticosteroid and immunosuppressive treatment. Isolated or multiple involvements of cardiac tunics should lead to make diagnosis of systemic vasculitis. A complete initial assessment and a close observation of the patients followed for Churg-Strauss syndrome is imperative to detect a cardiac achievement and set up an early treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Autoimmune Myocarditis, Valvulitis, and Cardiomyopathy

PubMed Central

Myers, Jennifer M.; Cunningham, Madeleine W.; Fairweather, DeLisa; Huber, Sally A.

2013-01-01

Cardiac myosin-induced autoimmune myocarditis (EAM) is a model of inflammatory heart disease initiated by CD4+ T cells (Smith and Allen 1991; Li, Heuser et al. 2004). It is a paradigm of the immune-mediated cardiac damage believed to play a role in the pathogenesis of a subset of postinfectious human cardiomyopathies (Rose, Herskowitz et al. 1993). Myocarditis is induced in susceptible mice by immunization with purified cardiac myosin (Neu, Rose et al. 1987) or specific peptides derived from cardiac myosin (Donermeyer, Beisel et al. 1995; Pummerer, Luze et al. 1996) (see Basic Protocol 1), or by adoptive transfer of myosin-reactive T cells (Smith and Allen 1991) (see Alternate Protocol). Myocarditis has been induced in Lewis rats by immunization with purified rat or porcine cardiac myosin (Kodama, Matsumoto et al. 1990; Li, Heuser et al. 2004) (see Basic Protocol 2) or S2-16 peptide (Li, Heuser et al. 2004), or by adoptive transfer of T cells stimulated by specific peptides derived from cardiac myosin (Wegmann, Zhao et al. 1994). Myocarditis begins 12 to 14 days after the first immunization, and is maximal after 21 days. Other animal models commonly used to study myocarditis development include the pathogen-induced models in which disease is initiated by viral infection. The first murine model of acute viral myocarditis causes sudden death via viral damage to cardiomyocytes (Huber, Gauntt et al. 1998; Horwitz, La Cava et al. 2000; Fong 2003; Fuse, Chan et al. 2005; Fairweather and Rose 2007; Cihakova and Rose 2008) whereas the second model is based on inoculation with heart-passaged coxsackievirus B3 (CVB3) that includes damaged heart proteins (Fairweather, Frisancho-Kiss et al. 2004; Fairweather D 2004; Fairweather and Rose 2007; Cihakova and Rose 2008) In addition to the protocols used to induce EAM in mice and rats, support protocols are included for preparing purified cardiac myosin using mouse or rat heart tissue (see Support Protocol 1), preparing purified cardiac myosin for injection (see Support Protocol 2), and collecting and assessing hearts by histopathological means (see Support Protocol 3). PMID:23564686

De novo development of eosinophilic myocarditis with left ventricular assist device support as bridge to transplant.

PubMed

Pereira, Naveen L; Park, Soon J; Daly, Richard C; Kushwaha, Sudhir S; Edwards, William D

2010-10-01

The de novo development of myocarditis during left ventricular assist device support for dilated cardiomyopathy has not been previously described. We report a case of severe eosinophilic myocarditis associated with the use of leukotriene-receptor antagonist montelukast that developed during left ventricular assist device support accompanied by intra-device thrombus formation that was hemodynamically tolerated and subsequently discovered in the explanted heart. There may be no visible change in cardiac function as assessed by echocardiography, but the diagnosis should be entertained with the development of peripheral eosinophilia. Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Cardiac MRI-confirmed mesalamine-induced myocarditis

PubMed Central

Baker, William L; Saulsberry, Whitney J; Elliott, Kaitlyn; Parker, Matthew W

2015-01-01

A 38-year-old Caucasian man with a medical history significant for inflammatory bowel disease (IBD) and mesalamine use presented to the emergency department with stabbing, pleuritic, substernal chest pain over the previous 2 days. Findings of leucocytosis, elevated cardiac enzymes and inflammatory markers, T-wave or ST-segment abnormalities and left ventricular systolic dysfunction suggested mesalamine-induced myocarditis. However, a cardiac MRI confirmed the diagnosis. Signs and symptoms improved within days of withdrawal of mesalamine, and initiation of corticosteroids and follow-up studies within the next year were unremarkable. Importantly, the diagnosis of mesalamine-induced myocarditis confirmed via cardiac MRI is a step rarely performed in published cases. PMID:26341161

Gallium-positive Lyme disease myocarditis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alpert, L.I.; Welch, P.; Fisher, N.

1985-09-01

In the course of a work-up for fever of unknown origin associated with intermittent arrhythmias, a gallium scan was performed which revealed diffuse myocardial uptake. The diagnosis of Lyme disease myocarditis subsequently was confirmed by serologic titers. One month following recovery from the acute illness, the abnormal myocardial uptake completely resolved.

Echocardiographic Changes in Eosinophilic Endocarditis Induced by Churg-Strauss Syndrome.

PubMed

Masaki, Nobuyuki; Issiki, Ami; Kirimura, Masato; Kamiyama, Tetsuo; Sasaki, Osamu; Ito, Hiroyuki; Maruyama, Yoshiaki; Nishioka, Toshihiko

Eosinophilic myocarditis may be accompanied by Churg-Strauss syndrome (CSS). We report a case of CSS that was accompanied by myocardial changes in the early stage. A 71-year-old woman complained of mild chest pain at rest, but routine echocardiography did not reveal any endocardial abnormalities. Four months later, the patient was hospitalized due to congestive heart failure with neuropathy of both upper extremities. A diagnosis of eosinophilic myocarditis was made based on the patient's laboratory results and the presence of mural thrombus. This case illustrates that, although early eosinophilic myocarditis is an important differential diagnosis in patients with chest pain, it may be difficult to identify in without an apparent mural thrombus.

Churg-Strauss syndrome presenting with eosinophilic myocarditis: a diagnostic challenge.

PubMed

Correia, Ana Sofia; Gonçalves, Alexandra; Araújo, Vítor; Almeida e Silva, João; Pereira, José Manuel; Rodrigues Pereira, Pedro; Pizarro, Manuel; Silva, João Carlos; Maciel, Maria Júlia

2013-09-01

Churg-Strauss syndrome (CSS) is an unusual disease that presents as systemic vasculitis and peripheral eosinophilia in patients with an atopic constitution. Cardiac involvement is unusual and often not prominent on initial presentation, but is an important cause of morbidity and mortality in patients with CSS. We report the case of a young woman with severe acute myocarditis. Coronary arteriography demonstrated extensive focal vasculopathy, consistent with coronary vasculitis, and myocardial biopsy showed eosinophilic myocarditis. This presentation led to an initial diagnosis of CSS in this patient and appropriate therapy resulted in a spectacular remission of disease activity. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Echocardiographic Changes in Eosinophilic Endocarditis Induced by Churg-Strauss Syndrome

PubMed Central

Masaki, Nobuyuki; Issiki, Ami; Kirimura, Masato; Kamiyama, Tetsuo; Sasaki, Osamu; Ito, Hiroyuki; Maruyama, Yoshiaki; Nishioka, Toshihiko

2016-01-01

Eosinophilic myocarditis may be accompanied by Churg-Strauss syndrome (CSS). We report a case of CSS that was accompanied by myocardial changes in the early stage. A 71-year-old woman complained of mild chest pain at rest, but routine echocardiography did not reveal any endocardial abnormalities. Four months later, the patient was hospitalized due to congestive heart failure with neuropathy of both upper extremities. A diagnosis of eosinophilic myocarditis was made based on the patient's laboratory results and the presence of mural thrombus. This case illustrates that, although early eosinophilic myocarditis is an important differential diagnosis in patients with chest pain, it may be difficult to identify in without an apparent mural thrombus. PMID:27725542

Cardiac MRI-confirmed mesalamine-induced myocarditis.

PubMed

Baker, William L; Saulsberry, Whitney J; Elliott, Kaitlyn; Parker, Matthew W

2015-09-04

A 38-year-old Caucasian man with a medical history significant for inflammatory bowel disease (IBD) and mesalamine use presented to the emergency department with stabbing, pleuritic, substernal chest pain over the previous 2 days. Findings of leucocytosis, elevated cardiac enzymes and inflammatory markers, T-wave or ST-segment abnormalities and left ventricular systolic dysfunction suggested mesalamine-induced myocarditis. However, a cardiac MRI confirmed the diagnosis. Signs and symptoms improved within days of withdrawal of mesalamine, and initiation of corticosteroids and follow-up studies within the next year were unremarkable. Importantly, the diagnosis of mesalamine-induced myocarditis confirmed via cardiac MRI is a step rarely performed in published cases. 2015 BMJ Publishing Group Ltd.

Two case reports of severe myocarditis associated with the initiation of dolutegravir treatment in HIV patients

PubMed Central

Mahlab-Guri, Keren; Asher, Ilan; Rosenberg-Bezalel, Shira; Elbirt, Daniel; Burke, Michael; Sthoeger, Zev M.

2016-01-01

Abstract Rationale: The integrase inhibitor dolutegravir is now recommended as first-line treatment for HIV. A single case of myocarditis after treatment with dolutegravir was reported in the FLAMINGO trial. We present here 2 cases of severe myocarditis that occurred shortly after the initiation of dolutegravir treatment. Patients concerns: The first case is a 45-year-old female who developed severe congestive heart failure and died, weeks after the initiation of dolutegravir treatment (for simplification of her antiretroviral regimen). The second case was a 51-year-old male who presented with effort dyspnea 3 weeks after the initiation of dolutegravir treatment and was later diagnosed as severe congestive heart failure. The treatment was changed and the patient survived, but he still suffers from severe heart failure with functional impairment. Diagnosis and Outcome: Patient 1 died, patient 2 suffers from severe heart failure. Lessons: We discuss here the possible relationship between the initiation of dolutegravir treatment and the development of lymphocytic myocarditis in our patients, and we suggest a possible mechanism. PMID:27893693

Identification of novel mimicry epitopes for cardiac myosin heavy chain-α that induce autoimmune myocarditis in A/J mice.

PubMed

Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Steffen, David; Reddy, Jay

2011-01-01

Myocarditis is one cause of sudden cardiac death in young adolescents, and individuals affected with myocarditis can develop dilated cardiomyopathy, a frequent reason for heart transplantation. Exposure to environmental microbes has been suspected in the initiation of heart autoimmunity, but the direct causal link is lacking. We report here identification of novel mimicry epitopes that bear sequences similar to those in cardiac myosin heavy chain (MYHC)-α 334-352. These epitopes represent Bacillus spp., Magnetospirillum gryphiswaldense, Cryptococcus neoformans and Zea mays. The mimicry peptides induced varying degrees of myocarditis in A/J mice reminiscent of the disease induced with MYHC-α 334-352. We demonstrate that the mimics induce cross-reactive T cell responses for MYHC-α 334-352 as verified by MHC class II IA(k)/tetramer staining and Th-1 and Th-17 cytokines similar to those of MYHC-α 334-352. The data suggest that exposure to environmental microbes which are otherwise innocuous can predispose to heart autoimmunity by molecular mimicry. Copyright © 2011 Elsevier Inc. All rights reserved.

Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis

PubMed Central

Robinson, Prema; Taffet, George E.; Engineer, Nikita; Khumbatta, Mitra; Firozgary, Bahrom; Reynolds, Corey; Pham, Thuy; Bulsara, Tushar; Firozgary, Gohar

2015-01-01

Viral-myocarditis is an important cause of heart failure for which no specific treatment is available. We previously showed the neuropeptide substance P (SP) is associated with the pathogenesis of murine myocarditis caused by encephalomyocarditis virus (EMCV). The current studies determined if pharmacological inhibition of SP-signaling via its high affinity receptor, NK1R and downstream G-protein, Ras homolog gene family, member-A (RhoA), will be beneficial in viral-myocarditis. Aprepitant (1.2 mg/kg), a SP-receptor antagonist, or fasudil (10 mg/kg), a RhoA inhibitor, or saline control was administered daily to mice orally for 3 days, prior to, or 5 days following, intraperitoneal infection with and without 50 PFU of EMCV, following which disease assessment studies, including echocardiogram and cardiac Doppler were performed in day 14 after infection. Pretreatment and posttreatment with aprepitant significantly reduced mortality, heart and cardiomyocyte size, and cardiac viral RNA levels (P < 0.05 all, ANOVA). Only aprepitant pretreatment improved heart functions; it significantly decreased end systolic diameter, improved fractional shortening, and increased peak aortic flow velocity (P < 0.05 all, ANOVA). Pre- or posttreatment with fasudil did not significantly impact disease manifestations. These findings indicate that SP contributes to cardiac-remodeling and dysfunction following ECMV infection via its high affinity receptor, but not through the Rho-A pathway. These studies suggest that SP-receptor antagonism may be a novel therapeutic-option for patients with viral-myocarditis. PMID:25821814

Heart Failure and Mortality of Adult Survivors from Acute Myocarditis Requiring Intensive Care Treatment - A Nationwide Cohort Study

PubMed Central

Chang, Jung-Jung; Lin, Ming-Shyan; Chen, Tien-Hsing; Chen, Dong-Yi; Chen, Shao-Wei; Hsu, Jen-Te; Wang, Po-Chang; Lin, Yu-Sheng

2017-01-01

Background The correlation between severity and long-term outcomes of pediatric myocarditis have been reported, however this correlation in adults has rarely been studied. Materials and Methods This nationwide population-based cohort study used data from the National Health Insurance Research Database in Taiwan. Patients aged < 75 and > 18 years admitted to an intensive care unit due to acute myocarditis were enrolled and divided into three groups according to mechanical circulatory support (MCS) after excluding major comorbidities. All-cause mortality, cardiovascular death, and heart failure hospitalization were evaluated from January 1, 2001 to December 31, 2011. Results There were 1145 patients with acute myocarditis (mean age 40.2 years, SD: 14.8 years), of which 851 did not require MCS, 99 underwent intra-aortic balloon pump (IABP) support, and 195 extracorporeal membrane oxygenation (ECMO) support. There was no significant difference in heart failure hospitalization between the three groups after index admission. The incidence of cardiovascular death after discharge ranged from 10 % to 22%, which was highest in the ECMO group, and was also significantly different between the three groups within 3 months (p<0.001) but it disappeared after 3 months (p=0.458). The trend was also noted in incidence of all-cause mortality. Conclusions The severity of acute myocarditis did not affect long-term outcomes, however, it was associated with cardiovascular/all-cause death within 3 months after discharge. PMID:29104480

Evaluation of left ventricular function by bedside ultrasound in acute toxic myocarditis.

PubMed

Brown, Cara; Budhram, Gavin

2013-10-01

Myocarditis can be difficult to diagnose in the Emergency Department (ED) due to the lack of classic symptoms and the wide variation in presentations. Poor cardiac contractility is a common finding in myocarditis and can be evaluated by bedside ultrasound. To demonstrate the utility of fractional shortening measurements as an estimation of left ventricular function during bedside cardiac ultrasound evaluation in the ED. A 54-year-old man presented to the ED complaining of 3 days of chest tightness, palpitations, and dyspnea, as well as persistent abdominal pain and vomiting. An electrocardiogram (ECG) showed sinus tachycardia with presumably new ST-segment elevation and signs of an incomplete right bundle branch block. A bedside echocardiogram was performed by the emergency physician that showed poor left ventricular function by endocardial fractional shortening measurements. On further questioning, the patient revealed that for the past 2 weeks he had been regularly huffing a commercially available compressed air duster. Based on these history and examination findings, the patient was given a presumptive diagnosis of toxic myocarditis. A follow-up echocardiogram approximately 7 weeks later demonstrated resolution of the left ventricular systolic dysfunction and his ECG findings normalized. Cardiac ultrasound findings of severely reduced global function measured by endocardial fractional shortening were seen in this patient and supported the diagnosis of myocarditis. Endocardial fractional shortening is a useful means of easily evaluating and documenting left ventricular function and can be performed at the bedside in the ED. Copyright © 2013 Elsevier Inc. All rights reserved.

TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-alpha blockade.

PubMed

Kroll-Palhares, Karina; Silvério, Jaline Coutinho; Silva, Andrea Alice da; Michailowsky, Vladimir; Marino, Ana Paula; Silva, Neide Maria; Carvalho, Cristiano Marcelo Espinola; Pinto, Luzia Maria de Oliveira; Gazzinelli, Ricardo Tostes; Lannes-Vieira, Joseli

2008-06-01

In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-alpha) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-alpha levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-alpha, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-alpha+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-alpha treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-alpha-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-alpha treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.

Mesenchymal Stromal Cells Modulate Monocytes Trafficking in Coxsackievirus B3‐Induced Myocarditis

PubMed Central

Miteva, Kapka; Pappritz, Kathleen; El‐Shafeey, Muhammad; Dong, Fengquan; Ringe, Jochen; Tschöpe, Carsten

2017-01-01

Abstract Mesenchymal stromal cell (MSC) application in Coxsackievirus B3 (CVB3)‐induced myocarditis reduces myocardial inflammation and fibrosis, exerts prominent extra‐cardiac immunomodulation, and improves heart function. Although the abovementioned findings demonstrate the benefit of MSC application, the mechanism of the MSC immunomodulatory effects leading to a final cardioprotective outcome in viral myocarditis remains poorly understood. Monocytes are known to be a trigger of myocardial tissue inflammation. The present study aims at investigating the direct effect of MSC on the mobilization and trafficking of monocytes to the heart in CVB3‐induced myocarditis. One day post CVB3 infection, C57BL/6 mice were intravenously injected with 1 x 106 MSC and sacrificed 6 days later for molecular biology and flow cytometry analysis. MSC application reduced the severity of myocarditis, and heart and blood pro‐inflammatory Ly6Chigh and Ly6Cmiddle monocytes, while those were retained in the spleen. Anti‐inflammatory Ly6Clow monocytes increased in the blood, heart, and spleen of MSC‐treated CVB3 mice. CVB3 infection induced splenic myelopoiesis, while MSC application slightly diminished the spleen myelopoietic activity in CVB3 mice. Left ventricular (LV) mRNA expression of the chemokines monocyte chemotactic protein‐1 (MCP)−1, MCP‐3, CCL5, the adhesion molecules intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, the pro‐inflammatory cytokines interleukin‐6, interleukin‐12, tumor necrosis factor‐α, the pro‐fibrotic transforming growth factorβ1, and circulating MCP‐1 and MCP‐3 levels decreased in CVB3 MSC mice, while LV stromal cell‐derived factor‐1α RNA expression and systemic levels of fractalkine were increased in CVB3 MSC mice. MSC application in CVB3‐induced myocarditis modulates monocytes trafficking to the heart and could be a promising strategy for the resolution of cardiac inflammation and prevention of the disease progression. Stem Cells Translational Medicine 2017;6:1249–1261 PMID:28186704

Fulminant fatal swine influenza (H1N1): Myocarditis, myocardial infarction, or severe influenza pneumonia?

PubMed

Cunha, Burke A; Syed, Uzma; Mickail, Nardeen

2010-01-01

The swine influenza (H1N1) pandemic began in Mexico and rapidly spread worldwide. As is the case with pandemic influenza A, the majority of early deaths have been in young healthy adults. The complications of pandemic H1N1 have been reported from several centers. Noteworthy has been the relative rarity of bacterial coinfection in bacterial pneumonia in hospitalized adults with H1N1 pneumonia. Simultaneous bacterial community-acquired pneumonia due to methicillin-sensitive Staphylococcus aureus or community-acquired methicillin resistant S. aureus and subsequent bacterial community-acquired pneumonia due to S. pneumoniae or Haemophilus influenzae have been reportedly rare (0.4%-4% of well-documented cases). Cardiac complications of H1N1 infection have been uncommon. Young healthy adults without a cardiac history who have H1N1 and chest pain usually have either acute myocardial infarction or acute myocarditis. Cardiac symptomatology with H1N1 often overshadows pulmonary manifestations, that is, influenza pneumonia. With H1N1 pneumonia, clinicians should be alert for otherwise unexplained tachycardia or chest pain that may represent acute myocardial infarction or myocarditis. We present a case of rapidly fatal H1N1 in a young adult treated with oseltamivir and peramivir. He was initially tachycardic, thought to represent myocarditis. He subsequently became hypotensive and expired. At autopsy there was cardiomegaly present but there were no signs of acute myocardial infarction or myocarditis. Pathologically, he died of severe H1N1 pneumonia and not bacterial pneumonia. Copyright © 2010 Elsevier Inc. All rights reserved.

A systematic review of validated methods to capture myopericarditis using administrative or claims data.

PubMed

Idowu, Rachel T; Carnahan, Ryan; Sathe, Nila A; McPheeters, Melissa L

2013-12-30

To identify algorithms that can capture incident cases of myocarditis and pericarditis in administrative and claims databases; these algorithms can eventually be used to identify cardiac inflammatory adverse events following vaccine administration. We searched MEDLINE from 1991 to September 2012 using controlled vocabulary and key terms related to myocarditis. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria. Two reviewers independently extracted data regarding participant and algorithm characteristics as well as study conduct. Nine publications (including one study reported in two publications) met criteria for inclusion. Two studies performed medical record review in order to confirm that these coding algorithms actually captured patients with the disease of interest. One of these studies identified five potential cases, none of which were confirmed as acute myocarditis upon review. The other study, which employed a search algorithm based on diagnostic surveillance (using ICD-9 codes 420.90, 420.99, 422.90, 422.91 and 429.0) and sentinel reporting, identified 59 clinically confirmed cases of myopericarditis among 492,671 United States military service personnel who received smallpox vaccine between 2002 and 2003. Neither study provided algorithm validation statistics (positive predictive value, sensitivity, or specificity). A validated search algorithm is currently unavailable for identifying incident cases of pericarditis or myocarditis. Several authors have published unvalidated ICD-9-based search algorithms that appear to capture myocarditis events occurring in the context of other underlying cardiac or autoimmune conditions. Copyright © 2013. Published by Elsevier Ltd.

Use of the Impella 5.0 Device as a Bridge to Recovery in Adult Fulminant Viral Myocarditis.

PubMed

Burns, Daniel J P; Quantz, Mackenzie A

2015-01-01

We present a case of a 48-year-old female patient successfully bridged to recovery with the Impella 5.0 microaxial pump (Abiomed, Danvers, MA USA) after presenting with cardiogenic shock secondary to acute fulminant viral myocarditis. After 1 week of flu-like symptoms, the patient presented to her community emergency department with chest pain and hypotension. A diagnosis of inferior ST elevation myocardial infarction was made; subsequent angiography demonstrated normal coronary arteries and a left ventricular ejection fraction of 10%. A provisional diagnosis of viral myocarditis was made. As her condition deteriorated further, she underwent insertion of an Impella 5.0 after failure of supportive medical therapy. Myocardial recovery occurred, and the Impella was removed after 1 week. After a prolonged cardiac intensive care unit stay requiring temporary hemodialysis, the patient recovered sufficiently to tolerate device explant, transfer to the recovery ward, and ultimate discharge home. This case report highlights the benefit of mechanical circulatory support in a patient with cardiogenic shock from viral myocarditis as well as some of the complications that can occur in this critically ill subset of patients.

A case report and literature review of Churg-Strauss syndrome presenting with myocarditis.

PubMed

Qiao, Lu; Gao, Dengfeng

2016-12-01

Churg-Strauss syndrome (CSS) is a multisystem disorder characterized by asthma, prominent peripheral blood eosinophilia, and vasculitis signs. Here we report a case of CSS presenting with acute myocarditis and heart failure and review the literature on CSS with cardiac involvement. A 59-year-old man with general fatigue, numbness of limbs, and a 2-year history of asthma was admitted to the department of orthopedics. Eosinophilia, history of asthma, lung infiltrates, peripheral neurological damage, and myocarditis suggested the diagnosis of CSS. Transthoracic echocardiography revealed a dilated hypokinetic left ventricle (left ventricular ejection fraction ∼40%) with mild segmental abnormalities in the septal and apical segments. By reviewing the present case reports, we concluded that (1) the younger age of CSS, the greater occurrence rate of complicating myocarditis and the poorer prognosis; (2) female CSS patients are older than male patients; (3) patients with cardiac involvement usually have a history of severe asthma; (4) markedly increased eosinophil count suggests a potential diagnosis of CSS (when the count increases to 20% of white blood cell counts or 8.1 × 109/L, eosinophils start to infiltrate into myocardium); and (5) negative ANCA status is associated with heart disease in CSS.

Toxic Myocarditis Caused by Acetaminophen in a Multidrug Overdose.

PubMed

Gosselin, Maxime; Dazé, Yann; Mireault, Pascal; Crahes, Marie

2017-12-01

We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction. A computed tomographic scan ruled out cerebral edema. The patient died of irreversible cardiac arrest 40 hours after admission. Heart failure remained unexplained, and the body underwent forensic autopsy.At autopsy, histologic findings were indicative of acute toxic myocarditis and were concluded to be caused by acetaminophen intoxication. Acetaminophen overdose is common and typically leads to liver failure requiring supportive treatment and emergency liver transplantation. Toxic myocarditis is an extremely rare complication of acetaminophen overdose. It has only been reported 4 times in the literature despite the widespread use and misuse of acetaminophen. Toxic myocarditis remains a possibility in many cases of overdose but can be overlooked in a clinical picture dominated by hepatorenal failure and encephalopathy. Clinicians and forensic pathologists should be aware of this rare potential complication.

Improved outcome of Trypanosoma cruzi infection in rats following treatment in early life with suspensions of heat-killed environmental Actinomycetales.

PubMed

Fontanella, G H; Pascutti, M F; Daurelio, L; Perez, A R; Nocito, A L; Wojdyla, D; Bottasso, O; Revelli, S S; Stanford, J L

2007-04-30

The well-established model of Chagas' disease in "l" rats was used to evaluate the effects of three injections of heat-killed Gordonia bronchialis, Rhodococcus coprophilus or saline on Trypanosoma cruzi parasitaemia and acute and chronic myocarditis, sequelae of the infection. Two vaccinating injections were given prior to challenge with T. cruzi, and the third, immunotherapeutic, injection was given 7 days after challenge. Treatment with either actinomycete significantly reduced acute parasitaemia (p<0.04), modified cellular infiltration during acute myocarditis and limited chronic myocarditis (p<0.03) in comparison with the saline-treated control animals. Immunological investigations showed that both bacterial preparations achieved their results through different mechanisms. The relevance of our findings to human Chagas' disease is discussed.

Normotensive cardiomyopathy and malignant hypertension in phaeochromocytoma

PubMed Central

Shapiro, L. M.; Trethowan, N.; Singh, S. P.

1982-01-01

A patient with two different presentations of phaeochromocytoma is described. She initially presented with normal blood pressure and heart failure following a prolonged feverish prodrome. A provisional diagnosis of myocarditis or early congestive cardiomyopathy was made and she improved with digoxin and diuretics. Eighteen months later, after a period of normotension free from heart failure, she developed malignant hypertension with recurrence of heart failure. A phaeochromocytoma was surgically removed, with return to normal of blood pressure and cardiac status. It would seem that the initial presentation of the phaeochromocytoma was a catecholamine-induced myocarditis without hypertension and this resolved with the subsequent development of malignant hypertension. The possible mechanisms responsible for this are discussed and it is concluded that phaeochromocytoma should be considered in patients who have heart failure and persistent features of myocarditis. PMID:7100023

A Risk Prediction Model for In-hospital Mortality in Patients with Suspected Myocarditis

PubMed Central

Xu, Duo; Zhao, Ruo-Chi; Gao, Wen-Hui; Cui, Han-Bin

2017-01-01

Background: Myocarditis is an inflammatory disease of the myocardium that may lead to cardiac death in some patients. However, little is known about the predictors of in-hospital mortality in patients with suspected myocarditis. Thus, the aim of this study was to identify the independent risk factors for in-hospital mortality in patients with suspected myocarditis by establishing a risk prediction model. Methods: A retrospective study was performed to analyze the clinical medical records of 403 consecutive patients with suspected myocarditis who were admitted to Ningbo First Hospital between January 2003 and December 2013. A total of 238 males (59%) and 165 females (41%) were enrolled in this study. We divided the above patients into two subgroups (survival and nonsurvival), according to their clinical in-hospital outcomes. To maximize the effectiveness of the prediction model, we first identified the potential risk factors for in-hospital mortality among patients with suspected myocarditis, based on data pertaining to previously established risk factors and basic patient characteristics. We subsequently established a regression model for predicting in-hospital mortality using univariate and multivariate logistic regression analyses. Finally, we identified the independent risk factors for in-hospital mortality using our risk prediction model. Results: The following prediction model for in-hospital mortality in patients with suspected myocarditis, including creatinine clearance rate (Ccr), age, ventricular tachycardia (VT), New York Heart Association (NYHA) classification, gender and cardiac troponin T (cTnT), was established in the study: P = ea/(1 + ea) (where e is the exponential function, P is the probability of in-hospital death, and a = −7.34 + 2.99 × [Ccr <60 ml/min = 1, Ccr ≥60 ml/min = 0] + 2.01 × [age ≥50 years = 1, age <50 years = 0] + 1.93 × [VT = 1, no VT = 0] + 1.39 × [NYHA ≥3 = 1, NYHA <3 = 0] + 1.25 × [male = 1, female = 0] + 1.13 × [cTnT ≥50 μg/L = 1, cTnT <50 μg/L = 0]). The area under the receiver operating characteristic curve was 0.96 (standard error = 0.015, 95% confidence interval [CI]: 0.93-0.99). The model demonstrated that a Ccr <60 ml/min (odds ratio [OR] = 19.94, 95% CI: 5.66–70.26), an age ≥50 years (OR = 7.43, 95% CI: 2.18–25.34), VT (OR = 6.89, 95% CI: 1.86–25.44), a NYHA classification ≥3 (OR = 4.03, 95% CI: 1.13–14.32), male gender (OR = 3.48, 95% CI: 0.99–12.20), and a cTnT level ≥50 μg/L (OR = 3.10, 95% CI: 0.91–10.62) were the independent risk factors for in-hospital mortality. Conclusions: A Ccr <60 ml/min, an age ≥50 years, VT, an NYHA classification ≥3, male gender, and a cTnT level ≥50 μg/L were the independent risk factors resulting from the prediction model for in-hospital mortality in patients with suspected myocarditis. In addition, sufficient life support during the early stage of the disease might improve the prognoses of patients with suspected myocarditis with multiple risk factors for in-hospital mortality. PMID:28345541

Myocardial oedema in acute myocarditis detected by echocardiographic 2D myocardial deformation analysis.

PubMed

Løgstrup, B B; Nielsen, J M; Kim, W Y; Poulsen, S H

2016-09-01

The clinical diagnosis of acute myocarditis is based on symptoms, electrocardiography, elevated myocardial necrosis biomarkers, and echocardiography. Often, conventional echocardiography reveals no obvious changes in global cardiac function and therefore has limited diagnostic value. Myocardial deformation imaging by echocardiography is an evolving method used to characterize quantitatively longitudinal systolic function, which may be affected in acute myocarditis. The aim of our study was to assess the utility of echocardiographic deformation imaging of the left ventricle in patients with diagnosed acute myocarditis in whom cardiovascular magnetic resonance (CMR) evaluation was performed. We included 28 consecutive patients (mean age 32 ± 13 years) with CMR-verified diagnosis of acute myocarditis according to the Lake Louise criteria. Cardiac function was evaluated by a comprehensive assessment of left ventricular (LV) function, including 2D speckle-tracking echocardiography. We found no significant correlation between the peak values of cardiac enzymes and the amount of myocardial oedema assessed by CMR (troponin: r= 0.3; P = 0.05 and CK-MB: r = 0.1; P = 0.3). We found a larger amount of myocardial oedema in the basal part of the left ventricle [American Heart Association (AHA) segments 1-6] in inferolateral and inferior segments, compared with the anterior, anterolateral, anteroseptal, and inferoseptal segments. In the mid LV segments (AHA segments 7-12), this was more pronounced in the anterior, anterolateral, and inferolateral segments. Among conventional echocardiographic parameters, LV function was not found to correlate with the amount of myocardial oedema of the left ventricle. In contrast, we found the wall motion score index to be significantly correlated with the amount of myocardial oedema, but this correlation was only present in patients with an extensive amount of oedema (>11% of the total left ventricle). Global longitudinal systolic myocardial strain correlated significantly with the amount of oedema (r = 0.65; P < 0.001). We found that both the epicardial longitudinal and the endocardial longitudinal systolic strains were significantly correlated with oedema (r = 0.55; P = 0.003 and r = 0.54; P < 0.001). In patients with acute myocarditis, 2D speckle-tracking echocardiography was a useful tool in the diagnostic process of acute myocarditis. Global longitudinal strain adds important information that can support clinical and conventional echocardiographic evaluation, especially in patients with preserved LV ejection fraction in relation to the diagnosis and degree of myocardial dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Effects of hepatocyte growth factor in myocarditis rats induced by immunization with porcine cardiac myosin

PubMed Central

Nakano, Jota; Marui, Akira; Muranaka, Hiroyuki; Masumoto, Hidetoshi; Noma, Hisashi; Tabata, Yasuhiko; Ido, Akio; Tsubouchi, Hirohito; Ikeda, Tadashi; Sakata, Ryuzo

2014-01-01

OBJECTIVES Myocarditis is considered one of the major causes of dilated cardiomyopathy. Hepatocyte growth factor (HGF) has pleiotropic activities that promote tissue regeneration and facilitate functional improvement of injured tissue. We investigated whether the epicardial sustained-release of HGF, using gelatin hydrogel sheets, improves cardiac function in a chronic myocarditis rat model. METHODS Six weeks after Lewis rats were immunized with porcine cardiac myosin to establish autoimmune myocarditis, HGF- or normal saline (NS)-incorporated gelatin hydrogel sheets were applied to the epicardium (G-HGF and G-NS, respectively). At either 2 or 4 weeks after treatment, these were compared with the Control myocarditis group. Cardiac function was evaluated by echocardiography and cardiac catheterization. Development of fibrosis was determined by histological study and expression of transforming growth factor-β1 (TGF-β1). Bax and Bcl-2 levels were measured to evaluate apoptotic activity. RESULTS At both points, fractional shortening and end-systolic elastance were higher in the G-HGF group than in the Control and G-NS groups (P < 0.01). Fractional shortening at 2 weeks of each group were as follows: 31.0 ± 0.9%, 24.8 ± 2.7% and 48.6 ± 2.6% (Control, G-NS and G-HGF, respectively). The ratio of the fibrotic area of the myocardium was lower in the G-HGF group than in the Control and G-NS groups at 2 weeks (G-HGF, 8.8 ± 0.9%; Control, 17.5 ± 0.2%; G-NS, 15.6 ± 0.7%; P < 0.01). The ratio at 4 weeks was lower in the G-HGF group than in the G-NS group (10.9 ± 1.4% vs 18.5 ± 1.3%; P < 0.01). The mRNA expression of TGF-β1 in the G-HGF group was lower than in the Control group at 2 weeks (0.6 ± 0.1 vs 1.1 ± 0.2) and lower than that in the G-NS group at 4 weeks (0.7 ± 0.1 vs 1.3 ± 0.2). The Bax-to-Bcl-2 ratios at both points were lower in the G-HGF group than in the Control group. CONCLUSIONS Sustained-released HGF markedly improves cardiac function in chronic myocarditis rats. The antifibrotic and antiapoptotic actions of HGF may contribute to the improvement. HGF-incorporated gelatin hydrogel sheet can be a new therapeutic modality for myocarditis. PMID:24327573

[Comparison analysis of muscle enzymes in children with myocarditis and Duchene/Becker muscular dystrophy].

PubMed

Zhang, Yali; Wang, Hong; Yu, Xuexin; Xing, Yanlin; Wang, Ce; He, Rong

2016-09-28

To compare the changes in muscle enzyme between children with myocarditis and Duchene/Becker muscular dystrophy (DMD/BMD), and to seek the explanations for variation.
 The retrospective analysis for 83 myocarditis children (myocarditis group) and 69 DMD/BMD children (DMD/BMD group), who were collected from Department of Pediatric of Shengjing Hospital affiliated to China Medical University since January 2008 to May 2015, was carried out. At the same time, 24 healthy children from the Department of Pediatric Development served as a control group. The examination indexes included creatine kinase (CK), creatine kinase-isoenzyme MB (CK-MB), creatine kinase isoenzyme MB mass (CK-MB mass), cardiac troponin I (cTnI) and high-sensitive-cTnT (hs-cTnT).
 1) In the myocarditis group, the CK increased from 100 to 1 000 U/L, reached a peak after 5 days, which lasted for a week and then dropped to the normal; the CK-MB reached a peak after 5 to 7 days and dropped to the normal a month later; the CK-MB mass reached a peak on the first day and dropped to the normal after 3 weeks; the cTn reached to a peak after 5 days and dropped to the normal after about 17 days; hs-cTnT reached to a peak on the first day and dropped to the normal after about 19 days. 2) In the DMD/BMD group, the CK increased significantly and 27 cases had a CK value of more than 10 000 U/L. After the treatment for 1 to 2 weeks, their enzyme rose again after a slight drop. In terms of cTnI, 6 cases showed a moderate increase, 5 of them couldn't drop to the normal level until more than 3 weeks later; the hs-cTnT increased in the 45 cases, which lasted for more than 3 weeks in the 31 cases of them and showed a tendency of persisting increase.
 The cTnI and hs-cTnT rise significantly and possess wider observation window than CK and CK-MB mass in myocarditis children, with more sensitive and specific changes. The myocardial damage can occur before myasthenia and keep this trend for a long time in the DMD/BMD children. The trend of cTnI change in myocarditis children is similar to hs-cTnT, while hs-cTnT in DMD/BMD children is more sensitive than cTnI.

[Bacteremia associated with mycotic aneurysm of the transversal aortic arch and myocarditis caused by Salmonella enteritidis].

PubMed

Martínez-Martínez, L; Mesa, E; Rodríguez, J E; Sánchez, M P; Ugarte, J; Algora Weber, A; Dámaso, D; Daza, R M; Mendaza, P

1989-02-01

A 60-year-old male with diabetes mellitus had Salmonella enteritidis bacteremia associated with mycotic aneurysm of the transverse aortic arc and myocarditis. Antibiotic therapy with ampicillin and chloramphenicol was ineffective despite the fact that the microorganism was sensitive in vitro to those antimicrobials, and the patient had a progressive clinical deterioration which culminated in death.

Hypersensitivity myocarditis associated with ephedra use.

PubMed

Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B

1999-01-01

Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

Vγ1+γδT, early cardiac infiltrated innate population dominantly producing IL-4, protect mice against CVB3 myocarditis by modulating IFNγ+ T response.

PubMed

Wan, Fangfang; Yan, Kepeng; Xu, Dan; Qian, Qian; Liu, Hui; Li, Min; Xu, Wei

2017-01-01

Viral myocarditis (VMC) is an inflammation of the myocardium closely associated with Coxsackievirus B3 (CVB3) infection. Vγ1 + γδT cells, one of early cardiac infiltrated innate population, were reported to protect CVB3 myocarditis while the precise mechanism not fully addressed. To explore cytokine profiles and kinetics of Vγ1 + γδT and mechanism of protection against VMC, flow cytometry was conducted on cardiac Vγ1 cells in C57BL/6 mice following CVB3 infection. The level of cardiac inflammation, transthoracic echocardiography and viral replication were evaluated after monoclonal antibody depletion of Vγ1γδT. We found that Vγ1 + γδT cells infiltration peaked in the heart at day3 post CVB3 infection and constituted a minor source of IFN-γ but major producers for early IL-4. Vγ1γδT cells were activated earlier holding a higher IL-4-producing efficiency than CD4 + Th cells in the heart. Depletion of Vγ1 + γδT resulted in a significantly exacerbated cardiac infiltration, increased T, macrophage and neutrophil population in heart homogenates and worse cardiomyopathy; which was accompanied by a significant expansion of peripheral IFNγ + CD4+ and CD8+T cells. Neutralization of IL-4 in mice resulted in an exacerbated acute myocarditis confirming the IL-4-mediated protective mechanism of Vγ1. Our findings identify a unique property of Vγ1 + γδT cells as one dominant early producers of IL-4 upon CVB3 acute infection which is a key mediator to protect mice against acute myocarditis by modulating IFNγ-secreting T response. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mesalamine-induced myocarditis following diagnosis of Crohn's disease: a case report.

PubMed

Galvão Braga, Carlos; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Vieira, Catarina; Salgado, Alberto; Magalhães, Sónia; Correia, Adelino

2013-09-01

Mesalamine is a common treatment for Crohn's disease, and can be rarely associated with myocarditis through a mechanism of drug hypersensitivity. We present the case of a 19-year-old male who developed chest pain two weeks after beginning mesalamine therapy. The electrocardiogram showed slight ST-segment elevation with upward concavity in the inferolateral leads; blood tests demonstrated elevated troponin I and the echocardiogram revealed moderately depressed left ventricular systolic function with global hypocontractility. Cardiac magnetic resonance imaging confirmed the diagnosis of myocarditis, revealing multiple areas of subepicardial fibrosis. The onset of symptoms after mesalamine, and improvement of chest pain, cardiac biomarkers and left ventricular systolic function after discontinuing the drug, suggest that our patient suffered from a rare drug-hypersensitivity reaction to mesalamine. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice.

PubMed

Kubo, Hisako; Hoshi, Masato; Mouri, Akihiro; Tashita, Chieko; Yamamoto, Yasuko; Nabeshima, Toshitaka; Saito, Kuniaki

2017-01-01

Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan - kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO -/- mice and KMO +/+ mice. KMO deficiency resulted in suppressed mortality after EMCV infection. The number of infiltrating cells and F4/80 + cells in KMO -/- mice was suppressed compared with those in KMO +/+ mice. KMO -/- mice showed significantly increased levels of serum KP metabolites, and induction of KMO expression upon EMCV infection was involved in its effect on mortality through EMCV suppression. Furthermore, KMO -/- mice showed significantly suppression of CCL2, CCL3 and CCL4 on day 2 and CXCL1 on day 4 after infection. These results suggest that increased KP metabolites reduced chemokine production, resulting in suppressed mortality upon KMO knockdown in EMCV infection. KP metabolites may thus provide an effective strategy for treating acute viral myocarditis. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.

PubMed

Zhang, Shouxin; Liu, Xiaoyan; Sun, Chengming; Yang, Jun; Wang, Lihong; Liu, Jie; Gong, Lei; Jing, Yanyan

2016-04-01

This study aims to investigate the protective effect of apigenin on the development of experimental autoimmune myocarditis (EAM) and the underlying mechanisms. An EAM model was induced in BALB/c mice by the injection of porcine cardiac myosin. Apigenin was orally administered from day 1 to 21. The severity of myocarditis was assessed by determination of heart weight/body weight ratio (HW/BW) and histopathological evaluation. Echocardiography was conducted to evaluate the cardiac function and heart structure. Antigen-specific T cell proliferation responses to cardiac myosin were evaluated by the lymphocyte proliferation assay. ELISA was used to determine serum levels of type 1 helper (Th1) and Th2 cytokines. Apigenin treatment significantly decreased HW/BW. Histopathologic analysis showed that the infiltration of inflammatory cells was reduced significantly by apigenin treatment. Meanwhile, apigenin administration effectively ameliorated autoimmune myocarditis-induced cardiac hypertrophy and cardiac dysfunction as well as inhibited lymphocyte proliferation in mice immunized with myosin. Furthermore, Th1 cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) were significantly downregulated, while Th2 cytokines IL-4 and IL-10 were markedly upregulated. The results indicated that apigenin can alleviate EAM due to its immunomodulatory reactions in modification of helper T cell balance.

A case report and literature review of Churg–Strauss syndrome presenting with myocarditis

PubMed Central

Qiao, Lu; Gao, Dengfeng

2016-01-01

Abstract Background: Churg–Strauss syndrome (CSS) is a multisystem disorder characterized by asthma, prominent peripheral blood eosinophilia, and vasculitis signs. Case summary: Here we report a case of CSS presenting with acute myocarditis and heart failure and review the literature on CSS with cardiac involvement. A 59-year-old man with general fatigue, numbness of limbs, and a 2-year history of asthma was admitted to the department of orthopedics. Eosinophilia, history of asthma, lung infiltrates, peripheral neurological damage, and myocarditis suggested the diagnosis of CSS. Transthoracic echocardiography revealed a dilated hypokinetic left ventricle (left ventricular ejection fraction ∼40%) with mild segmental abnormalities in the septal and apical segments. Conclusion: By reviewing the present case reports, we concluded that (1) the younger age of CSS, the greater occurrence rate of complicating myocarditis and the poorer prognosis; (2) female CSS patients are older than male patients; (3) patients with cardiac involvement usually have a history of severe asthma; (4) markedly increased eosinophil count suggests a potential diagnosis of CSS (when the count increases to 20% of white blood cell counts or 8.1 × 109/L, eosinophils start to infiltrate into myocardium); and (5) negative ANCA status is associated with heart disease in CSS. PMID:28002315

T1 and T2 mapping in myocarditis: seeing beyond the horizon of Lake Louise criteria and histopathology.

PubMed

Puntmann, Valentina O; Zeiher, Andreas M; Nagel, Eike

2018-05-01

Myocarditis and its sequelae remain an unconquered clinical problem, disproportionately affecting the young. Several hurdles beset myocarditis, including non-specific symptoms, heterogeneous clinical presentation, dynamic disease stages, underscored by an absence of an easy diagnostic test or a specific treatment. Areas covered: The current diagnostic means are poorly equipped to counter the challenge; the gold standard by invasive endomyocardial biopsy relies on availability of expert procedural and reading skill. The tissue diagnostic criteria were developed to improve readers agreement with clinical diagnosis, and not based on evidence for differential treatment or improved prognosis. The Lake-Louise Criteria represented a first step towards a non-invasive diagnosis. They require extensive imaging, which is insufficiently robust with poor diagnostic confidence and tissue pathophysiological validation; they similarly lack evidence of improved outcome by guiding clinical management. T1 and T2 mapping are a step-change, providing robust, short and quantifiable imaging application, which can veritably reflect the dynamic and heterogeneous underlying disease. Expert commentary: T1 and T2 mapping harbours a unique potential for an objective non-invasive disease recognition and treatment discovery in myocarditis. These measures should enter independently into clinical experimentation, with a high priority for outcome and therapeutic studies.

ISOLATION OF STREPTOCOCCI FROM A FATAL CASE OF MYOCARDITIS IN A CAPTIVE BROWN BEAR (URSUS ARCTOS).

PubMed

Ipek, Volkan; Gocmen, Huban; Cangul, I Taci

2017-03-01

A 10-yr-old, male brown bear ( Ursus arctos ) from Bursa Zoo in Turkey died without any apparent signs. Severe purulent pericarditis and myocarditis with mild ascites, lung edema, and moderate liver congestion were observed during necropsy. Microscopically, there were severe neutrophilic infiltrations in the myocardium and thoracic lymph nodes. A member of the Streptococcus bovis - Streptococcus equinus complex (SBSEC) was isolated and identified phenotypically.

[The quantum gravitational therapy of myocarditis].

PubMed

Ovcharova, A P

1999-01-01

Complex therapy of myocarditis of rheumatic and non-rheumatic genesis using intravascular laser irradiation of blood, quercitrol, and enterosgel has an antiinflammatory, antioxidant action, improves myocardial contractility, is endowed with an antiaggregatory activity. The above therapeutic complex permits the reduction of the non-steroid antiinflammatory drugs intake as well as of the average time of hospital treatment by 2 to 3 days, it also makes for an earlier medical and social rehabilitation of patients.

Salmonella myocarditis in a young adult patient presenting with acute pulmonary edema, rhabdomyolysis, and multi-organ failure.

PubMed

Al-aqeedi, Rafid Fayadh; Kamha, Ahmed; Al-aani, Fuad K; Al-ani, Ahmed A

2009-12-01

The mortality and morbidity of salmonella infections is seriously underestimated. Salmonella myocarditis is an unusual complication of salmonella sepsis in adults. Cases that do occur may be associated with high morbidity and mortality. We present a rare case of salmonella myocarditis with multi-organ failure in a previously healthy young adult man who was brought to the emergency room with fever, diarrhea, shortness of breath, and altered sensorium, discovered to have acute pulmonary edema and respiratory compromise for which he was assisted with mechanical ventilation for 8 days. Blood culture grew Salmonella typhi. Biochemically he exhibited myocardial, hepatic, and muscular enzymatic surge with renal failure, features of rhabdomyolysis, and disseminated intravascular coagulation. The patient showed a progressive improvement on treatment with ceftriaxone for 2 weeks in addition to decongestive therapy. He was discharged in good condition afterward.

Myositis, Ganglioneuritis, and Myocarditis with Distinct Perifascicular Muscle Atrophy in a 2-Year-Old Male Boxer

PubMed Central

Rossman, Paul M.; Thomovsky, Stephanie A.; Schafbuch, Ryan M.; Guo, Ling T.; Shelton, G. D.

2018-01-01

A 2-year-old male, intact Boxer was referred for chronic diarrhea, hyporexia, labored breathing, weakness and elevated creatine kinase, and alanine aminotransferase activities. Initial examination and diagnostics revealed a peripheral nervous system neurolocalization, atrial premature complexes, and generalized megaesophagus. Progressive worsening of the dog’s condition was noted after 36 h; the dog developed aspiration pneumonia, was febrile and oxygen dependent. The owners elected humane euthanasia. Immediately postmortem biopsies of the left cranial tibial and triceps muscles and the left peroneal nerve were obtained. Postmortem histology revealed concurrent myositis, myocarditis, endocarditis, and ganglioneuritis. Mixed mononuclear cell infiltrations and a distinct perifascicular pattern of muscle fiber atrophy was present in both muscles. This is a novel case of diffuse inflammatory myopathy with a distinct perifascicular pattern of atrophy in addition to endocarditis, myocarditis, and epicarditis. PMID:29516006

Sex and Gender Differences in Myocarditis and Dilated Cardiomyopathy

PubMed Central

Fairweather, DeLisa; Cooper, Leslie T; Blauwet, Lori A

2014-01-01

Heart failure due to nonischemic dilated cardiomyopathy (DCM) contributes significantly to the global burden of cardiovascular disease. Myocarditis is in turn a major cause of acute dilated cardiomyopathy in both men and women. However, recent clinical and experimental evidence suggests that the pathogenesis and prognosis of DCM differ between the sexes. This seminar provides a contemporary perspective on the immune mediators of myocarditis, including interdependent elements of the innate and adaptive immune response. The heart's acute response to injury is influenced by sex hormones that appear to determine the subsequent risk of chronic DCM. Preliminary data suggest additional genetic variations may account for some of the differences in epidemiology, left ventricular recovery and survival between men and women. We highlight the gaps in our knowledge regarding the management of women with acute DCM and discuss emerging therapies, including bromocriptine for the treatment of peripartum cardiomyopathy. PMID:23158412

Juvenile Churg-Strauss Syndrome as an Etiology of Myocarditis and Ischemic Stroke in Adolescents; a Case Report

PubMed Central

Moradinejad, Mohammad-Hassan; Rezaei, Amir; Ziaee, Vahid

2011-01-01

Background Churg-Strauss syndrome (CSS), a systemic vasculitis accompanied by asthma and eosinophilia, almost invariably affects the lung and is frequently associated with cutaneous involvement. It rarely has cardiac involvement. We report an unusual case of CSS with myocardial involvement and stroke. Case Presentation A 16-year old female suffered of allergic asthma for 4 years. She was under treatment with oral prednisolone and seretide inhalation. After CSS diagnosis, she developed paroxysmal atrial tachycardia. Serum levels of Troponin I and Troponin T were increased indicating massive myocardial damage probably due to myocarditis. After 5 months she developed acute hemiparesis without any evidence of ischemic or hemorrhagic event. She was treated with IVIg, intravenous pulses of methylprednisone and cyclophosphamide for each complication. Conclusion Myocarditis and stroke may also complicate CSS which should be taken in consideration for better management. PMID:23056844

A case of an unexplained eosinophilic myocarditis in a dog.

PubMed

Keeshen, T P; Chalkley, M; Stauthammer, C

2016-09-01

An 8-year-old spayed female Munsterlander was evaluated for a chronic low grade fever and a two month history of exercise intolerance. On physical examination, tachycardia and a grade II/VI right systolic heart murmur were detected. Echocardiography revealed marked thickening of the atrial and ventricular walls with mixed echogenicity and concentric hypertrophy of the left and right ventricles and equivocal systolic dysfunction. Serum cardiac troponin I level was markedly elevated. Endomyocardial biopsy was attempted; however, the patient arrested during the procedure and resuscitation was unsuccessful. Post-mortem examination revealed severe, chronic atrial and ventricular eosinophilic myocarditis associated with marked interstitial fibrosis. Serological testing, histopathology and immunohistochemistry staining did not reveal an underlying infectious agent or neoplasm. To our knowledge, this is the first reported case of primary eosinophilic myocarditis in the absence of a peripheral eosinophilia and multi-organ eosinophilic inflammation in a dog. Published by Elsevier B.V.

Pathogenesis of coxsackievirus B2 in mice: characterization of clinical isolates of the coxsackievirus B2 from patients with myocarditis and aseptic meningitis in Korea.

PubMed

Hong, Jiyoung; Kang, Bunghak; Yeo, Sanggu; Jee, Youngmee; Park, Jae-Hak

2017-12-31

Group B coxsackieviruses (CVBs) are a group of common human pathogens producing various clinical symptoms. Although the virology of CVB is well known, there is limited information on viral pathogenesis and the relationship between clinical symptoms and viral phenotype, particularly for CVB type 2 (CVB2). In 2004 in Korea, two CVB2 strains were isolated: CB2/04/279 from stool of an acute myocarditis patient with heart failure and CB2/04/243 from an aseptic meningitis patient. In this study, a high degree of homology was observed between the CB2/04/279 and CB2/04/243 full genome sequences. The two Korean CVB2 isolates had 93.1% homology compared to 82.1%-82.5% nucleotide sequence identity with the cardiovirulence-associated reference CVB strain Ohio-1 (CVB/O). CVB2-induced pathogenesis was analyzed, focusing on virus-induced pathology of various tissues in 4-week-old BALB/c inbred male mice. Myocarditis developed and extensive pancreatic inflammation was observed in all mice infected with CB2/04/279 or CVB/O, but not in animals infected with CB2/04/243. This is the first report of the full-genomic sequence and pathogenesis of the CVB2 strain isolated from an acute myocarditis patient in Korea.

Mononuclear cell secretome protects from experimental autoimmune myocarditis

PubMed Central

Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan

2015-01-01

Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. PMID:23321350

Pathogenic Role of the Damage-Associated Molecular Patterns S100A8 and S100A9 in Coxsackievirus B3-Induced Myocarditis.

PubMed

Müller, Irene; Vogl, Thomas; Pappritz, Kathleen; Miteva, Kapka; Savvatis, Konstantinos; Rohde, David; Most, Patrick; Lassner, Dirk; Pieske, Burkert; Kühl, Uwe; Van Linthout, Sophie; Tschöpe, Carsten

2017-11-01

The alarmins S100A8 and S100A9 are damage-associated molecular patterns, which play a pivotal role in cardiovascular diseases, inflammation, and viral infections. We aimed to investigate their role in Coxsackievirus B3 (CVB3)-induced myocarditis. S100A8 and S100A9 mRNA expression was 13.0-fold ( P =0.012) and 5.1-fold ( P =0.038) higher in endomyocardial biopsies from patients with CVB3-positive myocarditis compared with controls, respectively. Elimination of CVB3 led to a downregulation of these alarmins. CVB3-infected mice developed an impaired left ventricular function and displayed an increased left ventricular S100A8 and S100A9 protein expression versus controls. In contrast, CVB3-infected S100A9 knockout mice, which are also a complete knockout for S100A8 on protein level, showed an improved left ventricular function, which was associated with a reduced cardiac inflammatory and oxidative response, and lower CVB3 copy number compared with wild-type CVB3 mice. Exogenous application of S100A8 to S100A9 knockout CVB3 mice induced a severe myocarditis similar to wild-type CVB3 mice. In CVB3-infected HL-1 cells, S100A8 and S100A9 enhanced oxidative stress and CVB3 copy number compared with unstimulated infected cells. In CVB3-infected RAW macrophages, both alarmins increased MIP-2 (macrophage inflammatory protein-2) chemokine expression, which was reduced in CVB3 S100A8 knockdown versus scrambled siRNA CVB3 cells. S100A8 and S100A9 aggravate CVB3-induced myocarditis and might serve as therapeutic targets in inflammatory cardiomyopathies. © 2017 American Heart Association, Inc.

Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide.

PubMed

Shimada, Kana; Okabe, Taka-aki; Mikami, Yu; Hattori, Miki; Fujita, Masatoshi; Kishimoto, Chiharu

2010-09-01

We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process. Copyright 2010 Elsevier Ltd. All rights reserved.

Experimental encephalomyocarditis virus infection in small laboratory rodents.

PubMed

Doi, K

2011-01-01

Encephalomyocarditis virus (EMCV) is a cardiovirus that belongs to the family Picornaviridae. EMCV is an important cause of acute myocarditis in piglets and of fetal death or abortion in pregnant sows. Small rodents, especially rats, have been suspected to be reservoir hosts or carriers. This virus also induces type 1 diabetes mellitus, encephalomyelitis, myocarditis, orchitis and/or sialodacryoadenitis in small laboratory rodents. This paper reviews the pathology and pathogenesis of experimental infection with EMCV in small laboratory rodents. Copyright © 2010 Elsevier Ltd. All rights reserved.

Four cases of acute chagasic myocarditis in French Guiana.

PubMed

Carme, B; Aune, I; Nguyen, G; Aznar, C; Beaudet, B

2001-01-01

The authors report four cases of acute chagasic myocarditis which had been diagnosed and treated in Cayenne, French Guiana, in the past 6 years. This French territory, which has the highest standard of living in South America, should be considered an area of risk for sporadic Chagas disease with epidemiologic features similar to those of the disease found in dense Amazon forest areas. Appropriate measures must be taken to screen and promptly manage Chagas disease in the French Guiana population.

DTU I isolates of Trypanosoma cruzi induce upregulation of Galectin-3 in murine myocarditis and fibrosis.

PubMed

Ferrer, María F; Pascuale, Carla A; Gomez, Ricardo M; Leguizamón, María S

2014-05-01

Chagas heart disease is a major public concern since 30% of infected patients develop cardiac alterations. The relationship between Trypanosoma cruzi discrete typing units (DTUs) and the biological properties exhibited by the parasite population has yet to be elucidated. In this study, we analysed the expression of α-smooth muscle actin (α-SMA) and galectin-3 (Gal-3) associated with cardiac extracellular matrix (ECM) remodelling a murine chronic cardiomyopathy induced by Tc I genotypes. We found the induction of myocarditis was associated with the upregulation of Col I, α-SMA, Gal-3, IFN-γ and IL-13, as analysed by q-PCR. In myocardial areas of fibrosis, the intensity of myocarditis and significant ECM remodelling correlated with the presence of Col I-, Gal-3- and α-SMA-positive cells. These results are promising for the further efforts to evaluate the relevance of Gal-3 in Chagas heart disease, since this galectin was proposed as a prognosis marker in heart failure patients.

Myocardial complications of immunisations.

PubMed

Helle, E P; Koskenvuo, K; Heikkilä, J; Pikkarainen, J; Weckström, P

1978-10-01

Immunisation may induce myocardial complications. In this pilot study clinical, electrocardiographic, chemical and immunological findings have been studied during a six weeks' follow-up after routine immunisation (mumps, polio, tetanus, smallpox, diphtheria and type A meningococcal disease) among 234 Finnish conscripts at the beginning of their military service. Serial pattern of ECG changes suggestive of myocarditis was recorded in eight of the 234 conscripts one to two weeks after vaccination against smallpox and diphtheria. Changes were mainly minor ST segment elevations and T wave inversions and usually they disappeared in a few weeks. The ECG positives more often had a history of atopy, and their mean body temperatures and heart rates after the vaccinations were higher than among the other subjects (p less than 0.01). However, clinical myocarditis was never noted, nor were immunological or enzymological changes different among the ECG positives. Thus in 3% of the study population, evidence of postvaccinal myocarditis was noted, based on serial ECG patterns, but without any other evidence of cardiac disease.

Necroptosis may be a novel mechanism for cardiomyocyte death in acute myocarditis.

PubMed

Zhou, Fei; Jiang, Xuejun; Teng, Lin; Yang, Jun; Ding, Jiawang; He, Chao

2018-05-01

In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3. These findings provide evidence that necroptosis plays a significant role in cardiomyocyte death and it is a major pathway for cell death in acute VMC. Blocking the necroptosis pathway may serve as a new therapeutic option for the treatment of acute viral myocarditis.

Coxsackievirus B3 vaccines: use as an expression vector for prevention of myocarditis.

PubMed

Henke, Andreas; Jarasch, Nadine; Wutzler, Peter

2008-12-01

Coxsackievirus B3 (CVB3), a member of the Picornaviridae family, is considered to be one of the most important infectious agents to cause virus-induced myocarditis. Despite improvements in studying virus pathology, structure and molecular biology, as well as the diagnosis of this disease, there is still no virus-specific drug or vaccine in clinical use. During the last 20 years many investigations have been performed to develop classic and modern immunization techniques against CVB3-induced heart disease. One promising approach among others includes the insertion of coding sequences of cytokines into the viral genome. The application of an IFN-gamma-expressing recombinant coxsackievirus vector is especially efficient against CVB3-induced myocarditis. Beside direct IFN-gamma-mediated antiviral effects, the local and simultaneous expression of IFN-gamma by the virus itself activates the immune system in a strong and long-lasting manner, which protects animals completely against subsequent lethal infections independently of the age of the immunized individual and the route of vaccine administration.

Mononuclear cell secretome protects from experimental autoimmune myocarditis.

PubMed

Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan

2015-03-14

Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiac Pathology and Molecular Epidemiology by Avian Leukosis Viruses in Japan

PubMed Central

Nakamura, Sayuri; Ochiai, Kenji; Ochi, Akihiro; Yabushita, Hiroki; Abe, Asumi; Kishi, Sayaka; Sunden, Yuji; Umemura, Takashi

2014-01-01

Epidemiological studies suggest that retroviruses, including human immunodeficiency virus type 1, are associated with cardiomyopathy and myocarditis, but a causal relationship remains to be established. We encountered unusual cardiomyocyte hypertrophy and mitosis in Japanese native fowls infected with subgroup A of the avian leukosis viruses (ALVs-A), which belong to the genus Alpharetrovirus of the family Retroviridae and mainly induce lymphoid neoplasm in chickens. The affected hearts were evaluated by histopathology and immunohistochemistry, viral isolation, viral genome sequencing and experimental infection. There was non-suppurative myocarditis in eighteen fowls and seven of them had abnormal cardiomyocytes, which were distributed predominantly in the left ventricular wall and showed hypertrophic cytoplasm and atypical large nuclei. Nuclear chains and mitosis were frequently noted in these cardiomyocytes and immunohistochemistry for proliferating cell nuclear antigen supported the enhancement of mitotic activity. ALVs were isolated from all affected cases and phylogenic analysis of envSU genes showed that the isolates were mainly classified into two different clusters, suggesting viral genome diversity. In ovo experimental infection with two of the isolates was demonstrated to cause myocarditis and cardiomyocyte hypertrophy similar to those in the naturally occurring lesions and cardiac hamartoma (rhabdomyoma) in a shorter period of time (at 70 days of age) than expected. These results indicate that ALVs cause myocarditis as well as cardiomyocyte abnormality in chickens, implying a pathogenetic mechanism different from insertional mutagenesis and the existence of retrovirus-induced heart disorder. PMID:24466146

Mucosal Immunization with High-Mobility Group Box 1 in Chitosan Enhances DNA Vaccine-Induced Protection against Coxsackievirus B3-Induced Myocarditis

PubMed Central

Wang, Maowei; Yue, Yan; Dong, Chunsheng; Li, Xiaoyun; Xu, Wei

2013-01-01

Coxsackievirus B3 (CVB3), a small single-stranded RNA virus, belongs to the Picornaviridae family. Its infection is the most common cause of myocarditis, with no vaccine available. Gastrointestinal mucosa is the major entry port for CVB3; therefore, the induction of local immunity in mucosal tissues may help control initial viral infections and alleviate subsequent myocardial injury. Here we evaluated the ability of high-mobility group box 1 (HMGB1) encapsulated in chitosan particles to enhance the mucosal immune responses induced by the CVB3-specific mucosal DNA vaccine chitosan-pVP1. Mice were intranasally coimmunized with 4 doses of chitosan-pHMGB1 and chitosan-pVP1 plasmids, at 2-week intervals, and were challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 immunization alone, coimmunization with chitosan-pHMGB1 significantly (P < 0.05) enhanced CVB3-specific fecal secretory IgA levels and promoted mucosal T cell immune responses. In accordance, reduced severity of myocarditis was observed in coimmunized mice, as evidenced by significantly (P < 0.05) reduced viral loads, decreased myocardial injury, and increased survival rates. Flow cytometric analysis indicated that HMGB1 enhanced dendritic cell (DC) recruitment to mesenteric lymph nodes and promoted DC maturation, which might partly account for its mucosal adjuvant effect. This strategy may represent a promising approach to candidate vaccines against CVB3-induced myocarditis. PMID:24027262

Sex-specific signaling through Toll-Like Receptors 2 and 4 contributes to survival outcome of Coxsackievirus B3 infection in C57Bl/6 mice

PubMed Central

2012-01-01

Background Coxsackievirus B3 (CVB3) induces myocarditis, an inflammatory heart disease, which affects men more than women. Toll-like receptor (TLR) signaling has been shown to determine the severity of CVB3-induced myocarditis. No direct role for signaling through TLR2 had been shown in myocarditis although published studies show that cardiac myosin is an endogenous TLR2 ligand and stimulates pro-inflammatory cytokine expression by dendritic cells in vitro. The goal of this study is to determine which TLRs show differential expression in CVB3 infected mice corresponding to male susceptibility and female resistance in this disease. Methods Male and female C57Bl/6 mice were infected with 102 PFU CVB3 and killed on day 3 or 6 post infection. Hearts were evaluated for virus titer, myocardial inflammation, and TLR mRNA expression by PCR array and microarray analysis. Splenic lymphocytes only were evaluated by flow cytometry for the number of TLR+/CD3+, TLR+/CD4+, TLR+F4/80+ and TLR+/CD11c+ subpopulations and the mean fluorescence intensity to assess upregulation of TLR expression on these cells. Mice were additionally treated with PAM3CSK4 (TLR2 agonist) or ultrapure LPS (TLR4 agonist) on the same day as CVB3 infection or 3 days post infection to confirm their role in myocarditis susceptibility. Results Despite equivalent viral titers, male C57Bl/6 mice develop more severe myocarditis than females by day 6 after infection. Microarray analysis shows a differential expression of TLR2 at day 3 with female mice having higher levels of TLR2 gene expression compared to males. Disease severity correlates to greater TLR4 protein expression on splenic lymphocytes in male mice 3 days after infection while resistance in females correlates to preferential TLR2 expression, especially in spleen lymphocytes. Treating male mice with PAM reduced mortality from 55% in control CVB3 infected animals to 10%. Treating female mice with LPS increased mortality from 0% in control infected animals to 60%. Conclusion CVB3 infection causes an up-regulation of TLR2 in female and of TLR4 in male mice and this differential expression between the sexes contributes to disease resistance of females and susceptibility of males. While previous reports demonstrated a pathogenic role for TLR4 this is the first report that TLR2 is preferentially up-regulated in CVB3 infected female mice or that signaling through this TLR directly causes myocarditis resistance. PMID:23241283

Myocarditis.

PubMed

Fung, Gabriel; Luo, Honglin; Qiu, Ye; Yang, Decheng; McManus, Bruce

2016-02-05

Viral myocarditis remains a prominent infectious-inflammatory disease for patients throughout the lifespan. The condition presents several challenges including varied modes of clinical presentation, a range of timepoints when patients come to attention, a diversity of approaches to diagnosis, a spectrum of clinical courses, and unsettled perspectives on therapeutics in different patient settings and in the face of different viral pathogens. In this review, we examine current knowledge about viral heart disease and especially provide information on evolving understanding of mechanisms of disease and efforts by investigators to identify and evaluate potential therapeutic avenues for intervention. © 2016 American Heart Association, Inc.

Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation.

PubMed

Medina, Tiago Silva; Oliveira, Gabriela Gonçalves; Silva, Maria Cláudia; David, Bruna Araújo; Silva, Grace Kelly; Fonseca, Denise Morais; Sesti-Costa, Renata; Frade, Amanda Farage; Baron, Monique Andrade; Ianni, Barbara; Pereira, Alexandre Costa; Chevillard, Christophe; Cunha-Neto, Edécio; Marin-Neto, José Antonio; Silva, João Santana

2017-01-01

The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi -induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi . Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi -induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi -induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi -infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we describe a novel regulatory mechanism where Ebi3 dampens cardiac inflammation by modulating the overproduction of IFN-γ, the bona fide culprit of Chagas disease cardiomyopathy.

Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation

PubMed Central

Medina, Tiago Silva; Oliveira, Gabriela Gonçalves; Silva, Maria Cláudia; David, Bruna Araújo; Silva, Grace Kelly; Fonseca, Denise Morais; Sesti-Costa, Renata; Frade, Amanda Farage; Baron, Monique Andrade; Ianni, Barbara; Pereira, Alexandre Costa; Chevillard, Christophe; Cunha-Neto, Edécio; Marin-Neto, José Antonio; Silva, João Santana

2017-01-01

The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we describe a novel regulatory mechanism where Ebi3 dampens cardiac inflammation by modulating the overproduction of IFN-γ, the bona fide culprit of Chagas disease cardiomyopathy. PMID:29033934

Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice.

PubMed

Stein, Elisabeth A; Pinkert, Sandra; Becher, Peter Moritz; Geisler, Anja; Zeichhardt, Heinz; Klopfleisch, Robert; Poller, Wolfgang; Tschöpe, Carsten; Lassner, Dirk; Fechner, Henry; Kurreck, Jens

2015-02-15

Coxsackievirus B3 (CVB3) is a major heart pathogen against which no therapy exists to date. The potential of a combination treatment consisting of a proteinaceous virus receptor trap and an RNA interference-based component to prevent CVB3-induced myocarditis was investigated. A soluble variant of the extracellular domain of the coxsackievirus-adenovirus receptor (sCAR-Fc) was expressed from an adenoviral vector and 2 short hairpin RNAs (shRdRp2.4) directed against CVB3 were delivered by an adeno-associated virus (AAV) vector. Cell culture experiments revealed additive antiviral activity of the combined application. In a CVB3-induced mouse myocarditis model, both components applied individually significantly reduced inflammation and viral load in the heart. The combination exerted an additive antiviral effect and reduced heart pathology. Hemodynamic measurement revealed that infection with CVB3 resulted in impaired heart function, as illustrated by a drastically reduced cardiac output and impaired contractility and relaxation. Treatment with either sCAR-Fc or shRdRp2.4 significantly improved these parameters. Importantly, the combination of both components led to a further significant improvement of heart function. Combination of sCAR-Fc and shRdRp2.4 exerted additive effects and was significantly more effective than either of the single treatments in inhibiting CVB3-induced myocarditis and preventing cardiac dysfunction. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Diagnostic contribution of cardiac magnetic resonance in patients with acute coronary syndrome and culprit-free angiograms.

PubMed

Kawecki, Damian; Morawiec, Beata; Monney, Pierre; Pellaton, Cyril; Wojciechowska, Celina; Jojko, Joanna; Basiak, Marcin; Przywara-Chowaniec, Brygida; Fournier, Stephane; Nowalany-Kozielska, Ewa; Schwitter, Juerg; Muller, Olivier

2015-01-14

In spite of robust knowledge about underlying ischemic myocardial damage, acute coronary syndromes (ACS) with culprit-free angiograms raise diagnostic concerns. The present study aimed to evaluate the additional value of cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests, for the differentiation of myocardial injury in patients with ACS and non-obstructed coronary arteries. Patients with ACS, elevated hs-TnT, and a culprit-free angiogram were prospectively enrolled into the study between January 2009 and July 2013. After initial evaluation with standard tests (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial infarction (AMI) in coronary angiogram, patients were referred for CMR with the suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non-injured myocardium as assessed by late gadolinium enhancement. Out of 5110 patients admitted with ACS, 75 had normal coronary angiograms and entered the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC. After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of unrecognized AMI. The study results suggest that the evaluation of patients with ACS and culprit-free angiogram should be complemented by a CMR examination, if available, because the initial work-up with non-CMR tests leads to a significant proportion of misdiagnosed AMI.

Fatal pyogranulomatous myocarditis in 10 Boxer puppies.

PubMed

Detmer, Susan E; Bouljihad, Mostafa; Hayden, David W; Schefers, Jeremy M; Armien, Anibal; Wünschmann, Arno

2016-03-01

Over a period of 5 years, 10 pure-bred Boxer puppies, 9-16 weeks old, were presented with a history of sudden death and were diagnosed with pyogranulomatous myocarditis. The myocarditis was characterized by a mixed infiltrate composed predominantly of neutrophils and macrophages. In our retrospective study, original case records and archived materials were examined. All dogs were positive for Borrelia burgdorferi on immunohistochemistry (IHC). There was no evidence of infectious agents in formalin-fixed, paraffin-embedded (FFPE) heart tissue sections stained with hematoxylin and eosin, Ziehl-Neelsen, Gram, Grocott methenamine silver, Warthin-Starry, Von Kossa, and Steiner-Chapman stains. IHC for Chlamydia sp., Toxoplasma gondii, Neospora caninum, West Nile virus, and canine parvovirus also yielded a negative result in all dogs. Polymerase chain reaction testing for vector-borne pathogens on heart tissue from 9 of the dogs (1 frozen and 8 FFPE samples) yielded positive results for 1 dog with B. burgdorferi as well as Anaplasma phagocytophilum in another dog. Subsequently, 2 additional cases were found in a French Bulldog and a French Bulldog-Beagle mix that had identical morphology, test results, age, and seasonality to these 10 Boxer dogs. The similarities in the seasonality, signalment of the affected dogs, and the gross and microscopic lesions suggest a common etiology. Positive IHC and morphologic similarities to human Lyme carditis indicate that B. burgdorferi is likely the agent involved. An additional consideration for these cases is the possibility of a breed-specific autoimmune myocarditis or potential predisposition for cardiopathogenic agents in young Boxers. © 2016 The Author(s).

Myocarditis caused by Feline Immunodeficiency Virus in Five Cats with Hypertrophic Cardiomyopathy.

PubMed

Rolim, V Machado; Casagrande, R Assis; Wouters, A Terezinha Barth; Driemeier, D; Pavarini, S Petinatti

2016-01-01

Viral infections have been implicated as the cause of cardiomyopathy in several mammalian species. This study describes hypertrophic cardiomyopathy (HCM) and myocarditis associated with feline immunodeficiency virus (FIV) infection in five cats aged between 1 and 4 years. Clinical manifestations included dyspnoea in four animals, one of which also exhibited restlessness. One animal showed only lethargy, anorexia and vomiting. Necropsy examination revealed marked cardiomegaly, marked left ventricular hypertrophy and pallor of the myocardium and epicardium in all animals. Microscopical and immunohistochemical examination showed multifocal infiltration of the myocardium with T lymphocytes and fewer macrophages, neutrophils and plasma cells. An intense immunoreaction for FIV antigen in the cytoplasm and nucleus of lymphocytes and the cytoplasm of some macrophages was observed via immunohistochemistry (IHC). IHC did not reveal the presence of antigen from feline calicivirus, coronavirus, feline leukaemia virus, feline parvovirus, Chlamydia spp. or Toxoplasma gondii. The results demonstrate the occurrence of FIV infection in inflammatory cells in the myocardium of five cats with myocarditis and HCM. Copyright © 2015 Elsevier Ltd. All rights reserved.

New drugs and new toxicities: pembrolizumab-induced myocarditis.

PubMed

Inayat, Faisal; Masab, Muhammad; Gupta, Sorab; Ullah, Waqas

2018-01-23

Pembrolizumab is an immune checkpoint inhibitor that significantly improves clinical outcomes in numerous solid organ malignancies. Despite successful therapeutic responses, this new drug comes with a constellation of adverse reactions. Herein, we chronicle the case of a patient with metastatic non-small-cell lung cancer treated with pembrolizumab. After two cycles, he developed new-onset dyspnoea on exertion. Electrocardiogram showed idioventricular rhythm with diffuse ST-segment elevations. Echocardiography revealed severe biventricular cardiac dysfunction. Based on diagnostic workup and exclusion of probable aetiologies, the patient was diagnosed with pembrolizumab-induced myocarditis. The treatment was initiated with corticosteroids and guideline-conform heart failure therapy. He demonstrated a marked clinical response with resolution of congestive heart failure symptoms. This article summarises the clinical evidence regarding the epidemiology, pathophysiology, clinical features, diagnostic modalities and management of patients with pembrolizumab-associated myocarditis. In addition, it highlights that programmed death receptor-1 inhibition can cause a spectrum of autoimmune adverse events requiring clinical monitoring and periodic screenings. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ga-67 citrate myocardial uptake in a patient with AIDS, toxoplasmosis, and myocarditis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Memel, D.S.; DeRogatis, A.J.; William, D.C.

1991-05-01

A 38-year-old man with AIDS presented with fever of unknown origin, splenomegaly, anemia, and thrombocytopenia. Admission laboratory data revealed a positive toxoplasmosis titer in the blood. The initial chest x-ray showed small bilateral pleural effusions, a normal cardiac silhouette, no infiltrates, and no interstitial edema. Ga-67 imaging revealed markedly abnormal uptake in the myocardium. A diagnosis of toxoplasmosis myocarditis was made based on laboratory and imaging data. The patient was treated for toxoplasmosis. No myocardial uptake of tracer was demonstrated on a follow-up Ga-67 scan, performed after completion of treatment for toxoplasmosis.

Speckle tracking imaging in inflammatory heart diseases.

PubMed

Leitman, Marina; Vered, Zvi; Tyomkin, Vladimir; Macogon, Boris; Moravsky, Gil; Peleg, Eli; Copel, Laurian

2018-05-01

Accurate diagnosis of acute myocarditis is important for the prognosis and risk stratification of these patients. Cardiac magnetic resonance (CMR) has become a major modality for diagnosis of myocarditis, but not widely available. In this study, we tried to evaluate regional and global longitudinal strain by speckle tracking echocardiography in patients with acute inflammatory myocardial diseases in correlation with CMR. Patients with suspected acute myocarditis were recruited prospectively. Clinical diagnosis was established based on clinical, electrocardiographic, laboratory and conventional echocardiographic data. All patients underwent CMR and repeat echocardiographic examination within 24 h of CMR. Echocardiographic examinations were analyzed offline with speckle tracking imaging software. Thirty-two patients with acute perimyocarditis and myopericarditis were included. Mean age was 29 ± 8, 30 males. All patients presented with chest pain and an abnormal electrocardiogram, in 28 ST elevation was found. Troponin was elevated in 30 and was 0.7 ± 0.5 ng/ml. Creatine kinase was 487 ± 319 U. LVEF was 56 ± 5%. Wall motion abnormalities were present in postero-lateral (53%), and inferior wall (21%). Delayed enhancement on CMR was found in 29 patients. Echocardiographic EF based on speckle tracking imaging correlated with CMR calculated EF. There was a positive correlation between the amplitude of regional strain and delayed enhancement, r = 0.52. Sensitivity and specificity of regional strain for prediction of delayed enhancement was 85 and 73% respectively. Speckle tracking imaging can help in the diagnosis of acute myocarditis when CMR is not readily available. Speckle tracking imaging based EF correlates with CMR calculated LVEF and with global strain.

Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform.

PubMed

Sharma, Arun; Marceau, Caleb; Hamaguchi, Ryoko; Burridge, Paul W; Rajarajan, Kuppusamy; Churko, Jared M; Wu, Haodi; Sallam, Karim I; Matsa, Elena; Sturzu, Anthony C; Che, Yonglu; Ebert, Antje; Diecke, Sebastian; Liang, Ping; Red-Horse, Kristy; Carette, Jan E; Wu, Sean M; Wu, Joseph C

2014-08-29

Viral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. A major causative agent for viral myocarditis is the B3 strain of coxsackievirus, a positive-sense RNA enterovirus. However, human cardiac tissues are difficult to procure in sufficient enough quantities for studying the mechanisms of cardiac-specific viral infection. This study examined whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. hiPSC-CMs were infected with a luciferase-expressing coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs for alterations in cellular morphology and calcium handling. Viral proliferation in hiPSC-CMs was quantified using bioluminescence imaging. Antiviral compounds including interferonβ1, ribavirin, pyrrolidine dithiocarbamate, and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with reported drug effects in previous studies. Mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways after interferonβ1 treatment. This study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to predict antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that can screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion. © 2014 American Heart Association, Inc.

Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

PubMed Central

Shijie, Zhu; Moriya, Junji; Yamakawa, Jun’ichi; Chen, Rui; Takahashi, Takashi; Sumino, Hiroyuki; Nakahashi, Takeshi; Iwai, Kunimitsu; Morimoto, Shigeto; Yamaguchi, Nobuo

2010-01-01

Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1 kg−1 day−1) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each, P < 0.05). HW and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis. PMID:20671770

The diagnostic value of two commercially available human cTnI assays in goat kids with myocarditis.

PubMed

Karapinar, Tolga; Eroksuz, Yesari; Hayirli, Armagan; Beytut, Enver; Kaynar, Ozgur; Baydar, Ersoy; Sozdutmaz, Ibrahim; Isidan, Hakan

2016-03-01

Cardiac troponin I (cTnI) is a peripheral blood marker for myocardial damage. Because of the unavailability of goat-specific cTnI assays human cTnI assays may be validated for detection of myocarditis in goat kids. The purpose of the study was to evaluate 2 commercially available human cTnI assays in goat kids with myocardial damage, and to determine the cTnI expression in cardiac muscle. Plasma cTnI concentrations were measured in healthy goat kids (n = 7) and goat kids with myocardial damage (n = 8) using the Beckman Coulter Access Accu TnI and the Biomérieux Vidas Ultra. The results were correlated with gross necropsy and histopathologic findings, and cTnI immunhistochemistry in cardiac tissue. Macro- and microscopic findings confirmed myocardial damage in the myocarditis group. Mean plasma cTnI concentration was significantly higher in the myocarditis group than in the healthy control group (104.82 vs 0.02 ng/mL). The overall mean plasma cTnI concentration measured by Biomérieux Vidas Ultra (61.75 ng/mL, 95% CI: 19.55-103.95) was comparable to the mean measured by Beckman Coulter Access Accu TnI (50.08 ng/mL, 95% CI: 24.11-76.06), and cTnI concentrations measured by these assays were highly correlated (r = .977) with a -6.2% bias. Both assays were precise and accurate. The human-specific Beckman Coulter Access Accu TnI and the Biomérieux Vidas Ultra can be used for diagnostic confirmation of myocardial damage in caprine medicine. © 2016 American Society for Veterinary Clinical Pathology.

Presence of Antigen-Experienced T Cells with Low Grade of Differentiation and Proliferative Potential in Chronic Chagas Disease Myocarditis

PubMed Central

Cabeza-Meckert, Patricia; Viotti, Rodolfo; Garelli, Fernando; Favaloro, Liliana E.; Favaloro, Roberto R.; Laguens, Rubén; Laucella, Susana A.

2014-01-01

Background The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20–30% of infected individuals but not until 10–20 years after the initial infection. We have previously shown that circulating interferon-γ-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis. Methodology/Principal Findings The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3+, CD4+, CD8+, CD45RO+) with a low grade of differentiation (CD27+, CD57−, CD45RA−, PD-1−). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3+ T cells, assessed by Ki67 staining, was found. Conclusions/Significance The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection. PMID:25144227

Use of venoarterial extracorporeal membrane oxygenation in fulminant chagasic myocarditis as a bridge to heart transplant

PubMed Central

Durães, André Rodrigues; Figueira, Fernando Augusto Marinho dos Santos; Lafayette, André Rabelo; Martins, Juliana de Castro Solano; Juliano Cavalcante de, Sá

2015-01-01

A 17-year-old Brazilian male presented with progressive dyspnea for 15 days, worsening in the last 24 hours, and was admitted in respiratory failure and cardiogenic shock, with multiple organ dysfunctions. Echocardiography showed a left ventricle ejection fraction of 11%, severe diffuse hypokinesia, and a systolic pulmonary artery pressure of 50mmHg, resulting in the need for hemodynamic support with dobutamine (20mcg/kg/min) and noradrenaline (1.7mcg/kg/min). After 48 hours with no clinical or hemodynamic improvement, an extracorporeal membrane oxygenation was implanted. The patient presented with hemodynamic, systemic perfusion and renal and liver function improvements; however, his cardiac function did not recover after 72 hours, and he was transfer to another hospital. Air transport was conducted from Salvador to Recife in Brazil. A heart transplant was performed with rapid recovery of both liver and kidney functions, as well as good graft function. Histopathology of the explanted heart showed chronic active myocarditis and amastigotes of Trypanosoma cruzi. The estimated global prevalence of T. cruzi infections declined from 18 million in 1991, when the first regional control initiative began, to 5.7 million in 2010. Myocarditis is an inflammatory disease due to infectious or non-infectious conditions. Clinical manifestation is variable, ranging from subclinical presentation to refractory heart failure and cardiogenic shock. Several reports suggest that the use of extracorporeal membrane oxygenation in patients presenting with severe refractory myocarditis is a potential bridging therapy to heart transplant when there is no spontaneous recovery of ventricular function. In a 6-month follow-up outpatient consult, the patient presented well and was asymptomatic. PMID:26761479

Unusual echocardiographic features seen in a case of giant cell myocarditis

PubMed Central

Kochar, Minisha; López-Candales, Angel; Ramani, Gautam; Rajagopalan, Navin; Edelman, Kathy

2008-01-01

The case of an 18-year-old college football player with a recent history of streptococcal pharyngitis who was experiencing progressive disabling dyspnea on exertion with easy fatigability and lack of stamina, and was taken to the hospital after a syncopal episode is described. The patient was initially diagnosed with heart failure and treated accordingly. However, because of a fulminant clinical deterioration, an endomyocardial biopsy was recommended, which showed focal giant cell transformation consistent with giant cell myocarditis. Treatment with methylprednisolone and cyclosporine was promptly initiated. Several apical clots were noted during treatment, but the patient attained full recovery with treatment. PMID:18987760

Unusual echocardiographic features seen in a case of giant cell myocarditis.

PubMed

Kochar, Minisha; López-Candales, Angel; Ramani, Gautam; Rajagopalan, Navin; Edelman, Kathy

2008-11-01

The case of an 18-year-old college football player with a recent history of streptococcal pharyngitis who was experiencing progressive disabling dyspnea on exertion with easy fatigability and lack of stamina, and was taken to the hospital after a syncopal episode is described. The patient was initially diagnosed with heart failure and treated accordingly. However, because of a fulminant clinical deterioration, an endomyocardial biopsy was recommended, which showed focal giant cell transformation consistent with giant cell myocarditis. Treatment with methylprednisolone and cyclosporine was promptly initiated. Several apical clots were noted during treatment, but the patient attained full recovery with treatment.

Filgrastim as a Rescue Therapy for Persistent Neutropenia in a Case of Dengue Hemorrhagic Fever with Acute Respiratory Distress Syndrome and Myocarditis

PubMed Central

Deepak, Desh; Garg, Rakesh; Pawar, Mridula; Banerjee, Neerja; Solanki, Rakesh; Maurya, Indubala

2011-01-01

Pathogenesis of dengue involves suppression of immune system leading to development of characteristic presentation of haematological picture of thrombocytopenia and leucopenia. Sometimes, this suppression in immune response is responsible for deterioration in clinical status of the patient in spite of all specific and supportive therapy. Certain drugs like steroids are used for rescue therapy in conditions like sepsis. We present a novel use of filgrastim as a rescue therapy in a patient with dengue hemorrhagic fever (DHF) with acute respiratory distress syndrome (ARDS), myocarditis, and febrile neutropenia and not responding to standard management. PMID:22606398

[Adult-onset Still's disease with pulmonary and cardiac involvement and response to intravenous immunoglobulin].

PubMed

Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues

2009-01-01

Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

Atlantic salmon reovirus infection causes a CD8 T cell myocarditis in Atlantic salmon (Salmo salar L.).

PubMed

Mikalsen, Aase B; Haugland, Oyvind; Rode, Marit; Solbakk, Inge Tom; Evensen, Oystein

2012-01-01

Heart and skeletal inflammation (HSMI) of farmed Atlantic salmon (Salmo salar L.) is a disease characterized by a chronic myocarditis involving the epicardium and the compact and spongious part of the heart ventricle. Chronic myositis of the red skeletal muscle is also a typical finding of HSMI. Piscine reovirus (PRV) has been detected by real-time PCR from farmed and wild salmon with and without typical changes of HSMI and thus the causal relationship between presence of virus and the disease has not been fully determined. In this study we show that the Atlantic salmon reovirus (ASRV), identical to PRV, can be passaged in GF-1 cells and experimental challenge of naïve Atlantic salmon with cell culture passaged reovirus results in cardiac and skeletal muscle pathology typical of HSMI with onset of pathology from 6 weeks, peaking by 9 weeks post challenge. ASRV replicates in heart tissue and the peak level of virus replication coincides with peak of heart lesions. We further demonstrate mRNA transcript assessment and in situ characterization that challenged fish develop a CD8+ T cell myocarditis.

Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10

PubMed Central

Nogueira, Luciana Gabriel; Santos, Ronaldo Honorato Barros; Ianni, Barbara Maria; Fiorelli, Alfredo Inácio; Mairena, Eliane Conti; Benvenuti, Luiz Alberto; Frade, Amanda; Donadi, Eduardo; Dias, Fabrício; Saba, Bruno; Wang, Hui-Tzu Lin; Fragata, Abilio; Sampaio, Marcelo; Hirata, Mario Hiroyuki; Buck, Paula; Mady, Charles; Bocchi, Edimar Alcides; Stolf, Noedir Antonio; Kalil, Jorge; Cunha-Neto, Edecio

2012-01-01

Background Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2–6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC. PMID:23150742

Serological and Molecular Biological Studies of Parvovirus B19, Coxsackie B Viruses, and Adenoviruses as Potential Cardiotropic Viruses in Bulgaria.

PubMed

Ivanova, Stefka Kr; Angelova, Svetla G; Stoyanova, Asya P; Georgieva, Irina L; Nikolaeva-Glomb, Lubomira K; Mihneva, Zafira G; Korsun, Neli St

2016-12-01

Inflammatory diseases of the heart (myocarditis, pericarditis) are commonly caused by viruses. Among the human cardiotropic viruses, parvovirus B19, Coxsackie B viruses, and adenoviruses play a leading role. The aim of the present study was to determine the presumptive causative role of parvovirus B19, Coxsackie B viruses, and adenoviruses in the development of myocarditis, pericarditis and dilated cardiomyopathy by demonstrating the presence of specific antiviral antibodies or viral DNA in patients' serum samples. We tested serum samples collected between 2010 and 2014 from 235 patients with myocarditis (n=108), pericarditis (n=79), myopericarditis (n=19), dilated cardiomyopathy (n=7), and fever of unknown origin accompanied by cardiac complaints (n=22). The mean age of patients with the standard deviation was 33 ± 18 years. Serological and molecular methods (ELISA for specific IgM/IgG antibodies to parvovirus B19 and IgM antibodies to Coxsackie B viruses and adenoviruses, and PCR for detection of parvovirus B19 in serum samples, respectively) were used in the study. Of all tested 235 serum samples, in 60 (25.5%) positive results for at least one of the three tested viruses were detected. Forty out of these 235 serum samples (17%) were Coxsackie B virus IgM positive. They were found in 17% (18/108) of the patients with myocarditis, in 15% (12/79) of those with pericarditis, in 16% (3/19) of those with myopericarditis and in 32% (7/22) in those with fever of unknown origin. The 63 Coxsackie B virus IgM negative patient's serum samples were tested by ELISA for presence of adenovirus IgM antibodies. Such were found in 4 patients with pericarditis and in 2 patients with fever of unknown origin. Every IgM negative sample (n=189) for Coxsackie B and adenovirus was further tested by ELISA for parvovirus B19 IgM/IgG antibodies. B19-IgM antibodies were detected in 14 patients (7.4%). The percentages for B19-IgM antibodies was 8% (7/90), 5% (3/63) and 31% (4/13) in the patients affected with myocarditis, pericarditis, and fever of unknown origin, respectively. Protective B19-IgG antibodies were found in 108 (57%) of the samples. A B19-PCR signal was detected in all the patients who were B19-IgM positive, and in only 1 patient with positive B19-IgG result, the latter presenting with dilated cardiomyopathy. The present study shows the involvement of Coxsackie B, parvovirus B19 and adenoviruses in the development of inflammatory diseases of the heart (myocarditis and pericarditis). It is the first ever study in the country that simultaneously analyzes the prevalence of the three major human cardiotropic viruses.

Lyme carditis. Electrophysiologic and histopathologic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reznick, J.W.; Braunstein, D.B.; Walsh, R.L.

1986-11-01

To further define the nature of Lyme carditis, electrophysiologic study and endomyocardial biopsy were performed in a patient with Lyme disease, whose principal cardiac manifestation was high-degree atrioventricular block. Intracardiac recording demonstrated supra-Hisian block and complete absence of an escape mechanism. Gallium 67 scanning demonstrated myocardial uptake, and right ventricular endomyocardial biopsy revealed active lymphocytic myocarditis. A structure compatible with a spirochetal organism was demonstrated in one biopsy specimen. It is concluded that Lyme disease can produce active myocarditis, as suggested by gallium 67 imaging and confirmed by endomyocardial biopsy. Furthermore, the presence of high-grade atrioventricular block in this diseasemore » requires aggressive management with temporary pacemaker and corticosteroid therapy.« less

Diagnosis of Exclusion: A Case Report of Probable Glatiramer Acetate-Induced Eosinophilic Myocarditis

PubMed Central

Michaud, Christopher J.; Bockheim, Heather M.; Daum, Timothy E.

2014-01-01

Importance. Medication-induced eosinophilia is an acknowledged, often self-limiting occurrence. Glatiramer acetate, a biologic injection used in the management of relapsing-remitting multiple sclerosis, is widely regarded as a safe and effective medication and lists eosinophilia as an infrequent side effect in its package insert. Contrary to reports of transient, benign drug-induced eosinophilia, we describe a case of probable glatiramer acetate-induced eosinophilia that ultimately culminated in respiratory distress, shock, and eosinophilic myocarditis. Observations. A 59-year-old female was admitted to the hospital after routine outpatient labs revealed leukocytosis (43,000 cells/mm3) with pronounced hypereosinophilia (63%). This patient had been using glatiramer acetate without complication for over 10 years prior to admission. Leukocytosis and hypereosinophilia persisted as a myriad of diagnostic evaluations returned negative, ultimately leading to respiratory depression, shock, and myocarditis. Glatiramer acetate was held for the first time on day 6 of the hospital stay with subsequent resolution of leukocytosis, hypereosinophilia, respiratory distress, and shock. Conclusions and Relevance. Glatiramer acetate was probably the cause of this observed hypereosinophilia and the resulting complications. Reports of glatiramer-induced eosinophilia are rare, and few case reports regarding medication-induced hypereosinophilia describe the severe systemic manifestations seen in this patient. PMID:25105037

Diagnosis of exclusion: a case report of probable glatiramer acetate-induced eosinophilic myocarditis.

PubMed

Michaud, Christopher J; Bockheim, Heather M; Nabeel, Muhammad; Daum, Timothy E

2014-01-01

Importance. Medication-induced eosinophilia is an acknowledged, often self-limiting occurrence. Glatiramer acetate, a biologic injection used in the management of relapsing-remitting multiple sclerosis, is widely regarded as a safe and effective medication and lists eosinophilia as an infrequent side effect in its package insert. Contrary to reports of transient, benign drug-induced eosinophilia, we describe a case of probable glatiramer acetate-induced eosinophilia that ultimately culminated in respiratory distress, shock, and eosinophilic myocarditis. Observations. A 59-year-old female was admitted to the hospital after routine outpatient labs revealed leukocytosis (43,000 cells/mm(3)) with pronounced hypereosinophilia (63%). This patient had been using glatiramer acetate without complication for over 10 years prior to admission. Leukocytosis and hypereosinophilia persisted as a myriad of diagnostic evaluations returned negative, ultimately leading to respiratory depression, shock, and myocarditis. Glatiramer acetate was held for the first time on day 6 of the hospital stay with subsequent resolution of leukocytosis, hypereosinophilia, respiratory distress, and shock. Conclusions and Relevance. Glatiramer acetate was probably the cause of this observed hypereosinophilia and the resulting complications. Reports of glatiramer-induced eosinophilia are rare, and few case reports regarding medication-induced hypereosinophilia describe the severe systemic manifestations seen in this patient.

Effect of intravenous immunoglobulin for fulminant myocarditis on in-hospital mortality: propensity score analyses.

PubMed

Isogai, Toshiaki; Yasunaga, Hideo; Matsui, Hiroki; Tanaka, Hiroyuki; Horiguchi, Hiromasa; Fushimi, Kiyohide

2015-05-01

Fulminant myocarditis (FM) is a rare but life-threatening disease. Intravenous immunoglobulin (IVIG) is not recommended for acute or chronic myocarditis in Western nations owing to the lack of rigorous evidence, but it is widely used in other countries, including Japan. This nationwide retrospective cohort study focused on evaluating the effect of IVIG in FM patients. Using the Diagnosis Procedure Combination database in Japan, we identified 603 FM patients aged ≥16 years who received mechanical circulatory support within 7 days after admission. We performed propensity score analyses to compare the in-hospital mortality and total costs between IVIG users (n = 220; 36.5%) and nonusers (n = 383; 63.5%). Among propensity score-matched patients (164 pairs), there was no significant difference in in-hospital mortality between IVIG users and nonusers (36.6% vs 37.2%; P = .909). A multivariable logistic regression analysis showed no significant association between IVIG use and in-hospital mortality (adjusted odds ratio 0.91; 95% confidence interval 0.52 to 1.58; P = .733). The median total costs were significantly higher for IVIG users than for nonusers (US $44,226 vs $33,280; P < .001). IVIG for FM was not significantly associated with a decrease in in-hospital mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping.

PubMed

Baeßler, Bettina; Schaarschmidt, Frank; Treutlein, Melanie; Stehning, Christian; Schnackenburg, Bernhard; Michels, Guido; Maintz, David; Bunck, Alexander C

2017-12-01

To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping. • A novel quantitative approach to myocardial oedema imaging in myocarditis was re-evaluated. • The T2-mapping-derived parameters maxT2 and madSD were compared to traditional Lake-Louise criteria. • Using maxT2 and madSD with dedicated cut-offs performs similarly to Lake-Louise criteria. • Adding maxT2 and madSD to LGE results in further increased diagnostic performance. • This novel approach has the potential to overcome the limitations of T2-mapping.

Immunomodulation by adoptive regulatory T-cell transfer improves Coxsackievirus B3-induced myocarditis.

PubMed

Pappritz, Kathleen; Savvatis, Konstantinos; Miteva, Kapka; Kerim, Bahtiyar; Dong, Fengquan; Fechner, Henry; Müller, Irene; Brandt, Christine; Lopez, Begoña; González, Arantxa; Ravassa, Susana; Klingel, Karin; Diez, Javier; Reinke, Petra; Volk, Hans-Dieter; Van Linthout, Sophie; Tschöpe, Carsten

2018-06-04

Regulatory T (T reg ) cells offer new therapeutic options for controlling undesired systemic and local immune responses. The aim of the current study was to determine the impact of therapeutic T reg administration on systemic and cardiac inflammation and remodeling in coxsackievirus B3 (CVB3) -induced myocarditis. Therefore, syngeneic T reg cells were applied intravenously in CVB3-infected mice 3 d after infection. Compared with CVB3 + PBS mice, CVB3 + T reg mice exhibited lower left ventricular (LV) chemokine expression, accompanied by reduced cardiac presence of proinflammatory Ly6C high CCR2 high Cx3Cr1 low monocytes and higher retention of proinflammatory Ly6C mid CCR2 high Cx3Cr1 low monocytes in the spleen. In addition, splenic myelopoiesis was reduced in CVB3 + T reg compared with CVB3 + PBS mice. Coculture of T reg cells with splenocytes isolated from mice 3 d post-CVB3 infection further demonstrated the ability of T reg cells to modulate monocyte differentiation in favor of the anti-inflammatory Ly6C low CCR2 low Cx3Cr1 high subset. T reg -mediated immunomodulation was paralleled by lower collagen 1 protein expression and decreased levels of soluble and insoluble collagen in LV of CVB3 + T reg compared with CVB3 + PBS mice. In agreement with these findings, LV systolic and diastolic function was improved in CVB3 + T reg mice compared with CVB3 + PBS mice. In summary, adoptive T reg transfer in the inflammatory phase of viral-induced myocarditis protects the heart against inflammatory damage and fibrosis via modulation of monocyte subsets.-Pappritz, K., Savvatis, K., Miteva, K., Kerim, B., Dong, F., Fechner, H., Müller, I., Brandt, C., Lopez, B., González, A., Ravassa, S., Klingel, K., Diez, J., Reinke, P., Volk, H.-D., Van Linthout, S., Tschöpe, C. Immunomodulation by adoptive regulatory T-cell transfer improves Coxsackievirus B3-induced myocarditis.

Lyme disease presenting with facial palsy and myocarditis mimicking myocardial infarction.

PubMed

Gilson, Julieta; Khalighi, Koroush; Elmi, Farhad; Krishnamurthy, Mahesh; Talebian, Amirsina; Toor, Rubinder S

2017-01-01

A 45-year-old woman presented with a sudden episode of typical chest pain, radiating to her neck. The patient denied premature coronary artery disease in the family. Initial EKG showed normal sinus rhythm with a 1 mm ST-elevation involving lead II and lead aVF and a 1 mm ST-depression in lead V1 with associated T-wave inversion. Initial Troponin I (normal <0.4 ng/mL) and CK-MB (normal <7.7 ng/mL) were elevated at 7.82 ng/mL and 55.2 ng/mL, respectively. Six hours later, Troponin I increased to 13.44 ng/mL and CK-MB to 75.7 ng/mL. The patient underwent cardiac catheterization which did not show any significant obstructive coronary artery disease. Two days later the patient developed right-sided facial palsy. Diagnosis of Lyme disease was confirmed by ELISA with positive IgM and IgG antibodies. Treatment with intravenous ceftriaxone and oral steroids was started. Eventually resolution of symptoms and, normalization of cardiac markers and EKG changes, were achieved. This is a rare case of Lyme myocarditis associated with markedly elevated Troponin I, normal left ventricle function, and an absence of conduction abnormalities. To the best of our knowledge, Lyme myocarditis mimicking acute coronary syndrome with such high levels of Troponin I and neurologic compromise has not been previously described. Lyme myocarditis may be a challenging diagnosis in endemic areas especially in patients with coronary artery disease risk factors, presenting with typical chest pain, EKG changes and positive cardiac biomarkers. Therefore, it should be considered a differential diagnosis in patients presenting with clinical symptoms suggestive of acute coronary syndrome. Abbreviations AV: Atrioventricular; CK-MB: Creatinine Kinase-MB; EKG: Electrocardiogram; ELISA: Enzyme-Linked Immunosorbent Assay; IgG: Immunoglobulin G; IgM: Immunoglobulin M.

ECG (image)

MedlinePlus

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, ranging from congenital heart disease in ... and myocarditis in adults. Several different types of electrocardiogram exist.

Infectious mononucleosis complicated by acute hepatitis and myocarditis: a response to corticosteroids

PubMed Central

Ghosal, Robin; Lewis, Keir E; Chandramouli, Sriram

2009-01-01

Infectious mononucleosis, or glandular fever, is a viral illness which commonly affects young adults. Symptoms can vary from sore throat, enlarged lymph glands, lethargy and weight loss to more serious clinical manifestations such as myocarditis or hepatitis. Treatment is usually conservative although there has been significant debate over the role of oral corticosteroids, especially in more serious cases. Evidence based medicine suggests that there is little to no role for steroids, but there are enough published case reports where steroid therapy has been potentially life saving that the debate continues. We present a case of a fit and well man who had significant multi-organ involvement secondary to infectious mononucleosis, and our experience of oral corticosteroid treatment. PMID:21686466

Myocardial involvement in rocky mountain spotted fever: a case report and review.

PubMed

Doyle, Amy; Bhalla, Karan S; Jones, James M; Ennis, David M

2006-10-01

Rocky Mountain Spotted Fever (RMSF), caused by Rickettia rickettsii, is a serious tickborne illness that is endemic in the southeastern United States. Although it is most commonly known as a cause of fever and rash, it can have systemic manifestations. The myocardium may rarely be involved, with symptoms that can mimic those of acute coronary syndromes. This report describes a case of serologically proven RMSF causing symptomatic myocarditis, manifested by chest pain, elevated cardiac enzyme levels, and decrease myocardial function. After treatment with antibiotics, the myocarditis resolved. Thus, although unusual, the clinician should be aware of myocardial disease in patients with appropriate exposure histories or other clinical signs of RMSF. Close monitoring and an aggressive approach are essential to reduce mortality rates.

Requirement for Pathogenic IL-23 Signaling Is Restricted to Initiation of Autoimmune Myocarditis

PubMed Central

Wu, Lei; Diny, Nicola L.; Ong, SuFey; Barin, Jobert G.; Hou, Xuezhou; Rose, Noel R.; Talor, Monica V.; Čiháková, Daniela

2016-01-01

Using a mouse model of experimental autoimmune myocarditis (EAM), we showed for the first time that IL-23 stimulation of CD4+ T cells is required only briefly at the initiation of GM-CFS-dependent cardiac autoimmunity. IL-23 signal, acting as a switch, turns on pathogenicity of CD4+ T cells, and becomes dispensable once autoreactivity is established. Il23a−/− mice failed to mount an efficient Th17 response to immunization, and were protected from myocarditis. However, remarkably, transient IL-23 stimulation ex vivo fully restored pathogenicity in otherwise nonpathogenic CD4+ T cells raised from Il23a−/− donors. Thus, IL-23 may no longer be necessary to uphold inflammation in established autoimmune diseases. In addition, we demonstrated that IL-23 induced GM-CSF mediates the pathogenicity of CD4+ T cells in EAM. The neutralization of GM-CSF abrogated cardiac inflammation. However, sustained IL-23 signaling is required to maintain IL-17A production in CD4+ T cells. Despite inducing inflammation in Il23a−/− recipients comparable to WT, autoreactive CD4+ T cells downregulated IL-17A production without persistent IL-23 signaling. This divergence on the controls of GM-CSF-dependent pathogenicity on one side and IL-17A production on the other side may contribute to the discrepant efficacies of anti-IL-23 therapy in different autoimmune diseases. PMID:26660726

Myocarditis

MedlinePlus

... and toxoplasma, including some that are transmitted by insects and can cause a condition called Chagas disease. ... of your skin as possible. Apply tick or insect repellents that contain DEET. Get your vaccines. Stay ...

Fatal Serratia marcescens meningitis and myocarditis in a patient with an indwelling urinary catheter.

PubMed

Johnson, J S; Croall, J; Power, J S; Armstrong, G R

1998-10-01

Serratia marcescens is commonly isolated from the urine of patients with an indwelling urinary catheter and in the absence of symptoms is often regarded as a contaminant. A case of fatal Serratia marcescens septicaemia with meningitis, brain abscesses, and myocarditis discovered at necropsy is described. The patient was an 83 year old man with an indwelling urinary catheter who suffered from several chronic medical conditions and from whose urine Serratia marcescens was isolated at the time of catheterisation. Serratia marcescens can be a virulent pathogen in particular groups of patients and when assessing its significance in catheter urine specimens, consideration should be given to recognised risk factors such as old age, previous antibiotic treatment, and underlying chronic or debilitating disease, even in the absence of clinical symptoms.

Piscine myocarditis virus (PMCV) in wild Atlantic salmon Salmo salar.

PubMed

Garseth, Ase Helen; Biering, Eirik; Tengs, Torstein

2012-12-27

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of sea-farmed Atlantic salmon Salmo salar L., but CMS-like lesions have also been found in wild Atlantic salmon. In 2010 a double-stranded RNA virus of the Totiviridae family, provisionally named piscine myocarditis virus (PMCV), was described as the causative agent of CMS. In the present paper we report the first detection of PMCV in wild Atlantic salmon. The study is based on screening of 797 wild Atlantic salmon by real-time RT-PCR. The samples were collected from 35 different rivers along the coast of Norway, and all individuals included in the study were classified as wild, based on visual appearance and scale reading. Two samples tested positive during PCR analysis, and the results were confirmed by sequencing.

Bundle Branch Block

MedlinePlus

... known cause. Causes can include: Left bundle branch block Heart attacks (myocardial infarction) Thickened, stiffened or weakened ... myocarditis) High blood pressure (hypertension) Right bundle branch block A heart abnormality that's present at birth (congenital) — ...

THE KEY VIRAL PLAYERS

EPA Science Inventory

A number of different types of human enteric viruses cause waterborne outbreaks when individuals are exposed to contaminated drinking and recreational waters. Members of the enterovirus group cause numerous diseases, including gastroenteritis, encephalitis, meningitis, myocard...

FATAL ENCEPHALOMYOCARDITIS VIRUS INFECTION IN AN AFRICAN SAVANNA ELEPHANT (LOXODONTA AFRICANA) IN A FRENCH ZOO.

PubMed

Lamglait, Benjamin; Joris, Antoine; Romey, Aurore; Bakkali-Kassimi, Labib; Lemberger, Karin

2015-06-01

A fatal case of encephalomyocarditis virus (EMCV) involving an African elephant ( Loxodonta africana ) occurred in November 2013 at the Réserve Africaine de Sigean, France. An adult female was found dead without any preliminary symptoms. Gross pathologic changes consisted of petechiae and hemorrhages on mucosae and internal organs, abundant transudate in the abdominal and pericardial cavities, and myocarditis. Histopathologic examination showed extensive degeneration and necrosis of ventricular cardiomyocytes with concurrent lymphoplasmocytic and eosinophilic infiltrate. An EMCV was isolated from several organs and considered the causative agent of the myocarditis. The same strain of virus was also isolated in rodents captured on zoo premises and considered to be the reservoir of the virus. To the authors' knowledge, this is the first EMCV case in a captive African elephant in Europe.

Kawasaki syndrome in an adult: endomyocardial histology and ventricular function during acute and recovery phases of illness.

PubMed

Marcella, J J; Ursell, P C; Goldberger, M; Lovejoy, W; Fenoglio, J J; Weiss, M B

1983-08-01

Kawasaki syndrome, an acute systemic inflammatory illness of unknown origin usually affecting children, may develop into a serious illness complicated by coronary artery aneurysms or myocarditis. This report describes an adult with Kawasaki syndrome studied by right ventricular endomyocardial biopsy and cardiac catheterization during the acute and recovery phases of illness. The initial biopsy specimen showed acute myocarditis and was associated with hemodynamic evidence of biventricular dysfunction, a severely depressed left ventricular ejection fraction and global hypokinesia. With time, there was spontaneous and rapid resolution of the inflammatory cell infiltrate with concurrent return to normal myocardial function. Right ventricular endomyocardial biopsy studies early in the course of the cardiac disease associated with Kawasaki syndrome may correlate with ventricular function and may be useful for monitoring immunosuppressive therapy in patients with this syndrome.

Death of Military Working Dogs Due to Bartonella vinsonii Subspecies berkhoffii Genotype III Endocarditis and Myocarditis.

PubMed

Shelnutt, Leslie M; Balakrishnan, Nandhakumar; DeVanna, Justin; Batey, Kenneth L; Breitschwerdt, Edward B

2017-03-01

As a result of extensive field-related activities, military working dogs (MWDs) have an increased occupational risk for acquiring vector-borne infectious diseases. Indirect fluorescent antibody, Bartonella alpha-proteobacteria growth medium enrichment culture, and 16-23S Bartonella intergenic transcribed spacer polymerase chain reaction were performed using blood, serum, or tissue specimens. Endocarditis was diagnosed in three MWDs infected with Bartonella vinsonii subspecies (subsp.) berkhoffii genotype III. One dog was also infected with Bartonella rochalimae. B. vinsonii subsp. berkhoffii genotype III may represent an occupational risk for MWDs that develop endocarditis or myocarditis. Comprehensive periodic screening for canine vector-borne infections, in particular occult infections caused by Bartonella spp, is prudent to avoid serious or life-threating illnesses. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Hemoadsorption in cardiac shock with biventricular failure and giant-cell myocarditis: A case report.

PubMed

Dogan, Günes; Hanke, Jasmin; Puntigam, Jakob; Haverich, Axel; Schmitto, Jan D

2018-05-01

Giant-cell myocarditis represents a rare and often fatal autoimmune disorder. Despite extracorporeal life support being a valid treatment option, alternatives to control the underlying inflammatory response remain sparse. A new hemoadsorption device (CytoSorb) has recently been introduced to treat patients with an excessive inflammatory response. A 57-year-old patient developed fulminant right heart failure, respiratory insufficiency, hemodynamic instability, and oliguric-anuric renal failure. An extracorporeal life support together with an Impella was implanted for circulatory support. Due to non-pulsatility, acontractility of the left ventricle and a heavily reduced right ventricular function, a left ventricular assist device implantation and change from extracorporeal life support to veno-pulmonary arterial extracorporeal membrane oxygenation was performed. Since adequate hemodynamic stabilization could not be achieved and due to increasing inflammatory mediators and bilirubin levels, the decision was made to additionally integrate a CytoSorb hemoadsorber into the system. The combined treatment resulted in a clear and steady improvement in hemodynamics and the inflammatory condition with marked reductions in all measured parameters throughout the treatment period. Metabolic acidosis resolved and liver function improved. Extracorporeal life support therapy represents a bridging approach to heart transplantation or to cardiac recovery and can be complemented by CytoSorb as an independent therapeutic option. The patient described herein with giant-cell myocarditis and fulminant cardiac failure who received substantial extracorporeal support in combination with CytoSorb hemoadsorption therapy benefited in terms of an improvement of organ function and his inflammatory situation.

Epsilon wave on an electronic loop in a case of arrhythmogenic right ventricular dysplasia with myocarditis: an updated definition of the Epsilon wave.

PubMed

Fontaine, Guy Hugues; Duthoit, Guillaume; Li, Guoliang; Andreoletti, L; Gandjbakhch, Estelle; Frank, Robert

2017-07-01

A young man presented with a history of myocarditis with palpitations and dizziness. He had implantation of a loop recorder that showed repetitive short episodes of VT. In addition, there were fragmented potentials immediately following the large and sharp electrograms (EGMs) before as well as after episodes of VT suggesting an Epsilon wave. This signal can be observed in multiple cardiac conditions including coronary artery disease. It was originally recorded on the epicardium as well as on the endocardium. However, in ARVD it can be defined as an electric signal observed after the end of the QRS complex in the right as opposed to the left precordial leads (difference ≥ 25 ms). It can also be an aid to the diagnosis of patients with ARVD who have other signs or symptoms suggesting ARVD including episodes of myocarditis. This potential consists of a slurring at the end of the QRS complex or an independent potential after the return to the isoelectric line. It can be better observed by increasing amplification of the ECG tracing as well as double speed using the Fontaine lead system. Epsilon wave too small to be recorded on the standard ECG can be extracted by Signal Averaging ECG SAECG). Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Treatment and prevention of experimental autoimmune myocarditis with CD28 superagonists.

PubMed

Wang, Shu; Liu, Jing; Wang, Min; Zhang, Jinghui; Wang, Zhaohui

2010-01-01

Experimental autoimmune myocarditis (EAM), a rodent model of human dilated cardiomyopathy (DCM), is mediated by an autoimmune mechanism. We investigated whether a CD28 superagonistic antibody selectively targeting CD4+CD25+ regulatory T cells (T(regs)) provides effective therapy for EAM. Four groups of 5 rats were used. The normal control group was immunized with PBS. The EAM group was immunized with porcine myosin. The experimental group was immunized with myosin and superagonistic CD28 antibody JJ316. The final group was immunized with myosin and an unrelated rat IgG. Autoantibody and IL-10 production, CD4+CD25+ cell levels, Foxp3 expression and cardiac histology were analyzed. Anti-myosin autoantibody levels were higher in the EAM and isotype control groups than the normal control group (p < 0.05), and reduced in the CD28-JJ316 group (p < 0.05). The levels of CD25+CD4+ cells, IL-10 and splenocyte Foxp3 expression were significantly lower in the EAM and isotype control groups versus the CD28-JJ316 group (p < 0.05). Infiltration of inflammatory cells was observed in the EAM and isotype control groups, whereas CD28-JJ316 ameliorated myocarditis. CD28 superagonists could be effective in EAM treatment by up-regulating Foxp3 expression and contributing to CD4+CD25+ T(reg) activation and expansion. The enhancement in IL-10 by CD28 superagonists also ameliorated the disease.

EPA METHODS FOR VIRUS DETECTION IN WATER

EPA Science Inventory

A number of different types of human enteric viruses cause waterborne outbreaks when individuals are exposed to contaminated drinking and recreational waters. Members of the enterovirus group cause numerous diseases, including gastroenteritis, encephalitis, meningitis, myocard...

BIOMARKERS OF VIRAL EXPOSURE

EPA Science Inventory

Viral and protozoan pathogens associated with raw sludge can cause encephalitis, gastroenteritis, hepatitis, myocarditis, and a number of other diseases. Raw sludge that has been treated to reduce these pathogens can be used for land application according to the regulations spec...

QUALITY ASSURANCE FOR METHODS TO DETECT HUMAN ENTERIC VIRUSES IN DRINKING WATER

EPA Science Inventory

Surface or groundwaters impacted by untreated or inadequately treated domestic wastes may contain human pathogenic viruses that cause hepatitis, gastroenteritis, meningitis, encephalitis, myocarditis, diabetes, conjunctivitis and temporary or permanent paralysis. These viruses c...

Severe necrotizing myocarditis caused by serratia marcescens infection in an axolotl (Ambystoma mexicanum).

PubMed

Del-Pozo, J; Girling, S; Pizzi, R; Mancinelli, E; Else, R W

2011-05-01

This report provides the first account of the pathological changes associated with infection by Serratia marcescens in an adult male axolotl. The infection resulted in septicaemia with severe multifocal necrotizing myocarditis. The latter lesion evolved to cardiac rupture, haemopericardium and death resulting from cardiac tamponade. This animal was exposed to higher than usual temperatures (24-25 °C) 2 weeks before the onset of disease and this may have resulted in immunocompromise and opportunistic bacterial infection. S. marcescens was isolated from the coelomic and pericardial cavity. Both isolates were identical and were resistant to β-lactam antibiotics, but not to aminoglycosides or fluoroquinolones. The production of red prodigiosin pigment by the bacterium suggested an environmental origin. Overall, the clinical and histopathological presentation suggests that S. marcescens should be included in the list of aetiological agents of the 'red-leg'/bacterial dermatosepticaemia syndrome of amphibians. Copyright © 2010 Elsevier Ltd. All rights reserved.

Abdominal and hepatic uptake of /sup 99m/Tc-pyrophosphate in neonatal necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caride, V.J.; Touloukian, R.J.; Ablow, R.C.

1981-04-01

Abdominal /sup 99m/Tc-pyrophosphate (/sup 99m/Tc-PYP) scans were obtained in 15 neonates: 12 with neonatal necrotizing enterocolitis (NEC), two with osteomyelitis, and one with myocarditis. Ten of the babies with NEC had at least one positive scan; of these 10 studies, seven (Group A) showed both diffuse abdominal uptake and localized hepatic activity, two (Group B) showed abdominal uptake and questionable hepatic uptake, and one (Group C) demonstrated diffuse abdominal uptake only. The other two babies with NEC had normal scans (Group D). All NEC patients had normal scans. A patient with myocarditis had hepatic uptake of /sup 99m/Tc-PYP while themore » abdominal scan in the two infants with osteomyelitis was normal. These preliminary observations suggest that further study of a relationship between abdominal scan findings and the course of NEC is warranted.« less

Myocardial inflammation, cellular death, and viral detection in sudden infant death caused by SIDS, suffocation, or myocarditis.

PubMed

Krous, Henry F; Ferandos, Christine; Masoumi, Homeyra; Arnold, John; Haas, Elisabeth A; Stanley, Christina; Grossfeld, Paul D

2009-07-01

The significance of minor myocardial inflammatory infiltrates and viral detection in SIDS is controversial. We retrospectively compared the demographic profiles, myocardial inflammation, cardiomyocyte necrosis, and myocardial virus detection in infants who died of SIDS in a safe sleep environment, accidental suffocation, or myocarditis. Formalin-fixed, paraffin-embedded myocardial sections were semiquantitatively assessed for CD3 lymphocytes and CD68 macrophages using immunohistochemistry and for cardiomyocyte cell death in H&E-stained sections. Enteroviruses and adenoviruses were searched for using PCR technology. The means of lymphocytes, macrophages, and necrotic cardiomyocytes were not statistically different in SIDS and suffocation cases. Enterovirus, not otherwise specified, was detected in one suffocation case and was the only virus detected in the three groups. Very mild myocardial lymphocyte and macrophage infiltration and scattered necrotic cardiomyocytes in SIDS are not pathologic, but may occur after the developing heart is exposed to environmental pathogens, including viruses.

Severe Sepsis and Acute Myocardial Dysfunction in an Adolescent with Chlamydia Trachomatis Pelvic Inflammatory Disease: A Case Report.

PubMed

Morgan, Ashley M; Roden, R Claire; Matson, Steven C; Wallace, Grant M; Lange, Hannah L H; Bonny, Andrea E

2018-04-01

Although generally asymptomatic, severe Chlamydia trachomatis (C. trachomatis) infections have been documented. C. trachomatis has been associated with myocarditis as well as sepsis. A 19-year-old girl with type 1 diabetes mellitus developed sudden-onset mental status change and shock after resolution of diabetic ketoacidosis. Abdominal and pelvic imaging showed uterine and adnexal inflammation, and pelvic examination confirmed a diagnosis of pelvic inflammatory disease. The patient was intubated, required vasopressor support, and developed severe biventricular myocardial dysfunction. Infectious myocarditis workup was negative. Nucleic acid amplification testing from vaginal discharge was positive for C. trachomatis and Trichomonas vaginalis and negative for Neisseria gonorrhoeae. C. trachomatis should be considered in the workup of septic shock, particularly in populations at high risk for sexually transmitted infections. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Antiviral Effects of Small Interfering RNA Simultaneously Inducing RNA Interference and Type 1 Interferon in Coxsackievirus Myocarditis

PubMed Central

Ahn, Jeonghyun; Ko, Ara; Jun, Eun Jung; Won, Minah; Kim, Yoo Kyum; Ju, Eun-Seon

2012-01-01

Antiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5′-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5′ end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases. PMID:22508300

Effect and Mechanism of QiShenYiQi Pill on Experimental Autoimmune Myocarditis Rats.

PubMed

Lv, Shichao; Wu, Meifang; Li, Meng; Wang, Qiang; Xu, Ling; Wang, Xiaojing; Zhang, Junping

2016-03-06

To observe the effect of QiShenYiQi pill (QSYQ) on experimental autoimmune myocarditis rats, and to explore its mechanism of action. Lewis rats underwent the injection of myocardial myosin mixed with Freund's complete adjuvant were randomized into 3 groups: model, valsartan, and QSYQ groups. Rats injected with phosphate-buffered saline (PBS) mixed with Freund's complete adjuvant were used as the control group. Rats were euthanized at 4 and 8 weeks, and we weighed rat body mass, heart mass, and left ventricular mass. Myocardium sections were stained with hematoxylin and eosin (H&E) and Masson trichrome. Myocardial TGF-β1 and CTGF protein expression was detected by immunohistochemistry, and myocardial TGF-β1 and CTGF mRNA expression was detected by real-time qPCR. QSYQ reduced HMI and LVMI, as well as the histological score of hearts and CVF, which further decreased over time, and its effect was significantly greater than that of valsartan at 4 and 8 weeks. After 4 weeks, QSYQ inhibited the protein and mRNA expression of TGF-β1 and CTGF, and its effect on lowering CTGF was significantly greater than that of valsartan. In addition, after 8 weeks, QSYQ also inhibited the protein and mRNA expression of CTGF, whereas there was no significant difference in the expression of myocardial TGF-β1. This study provides evidence that QSYQ can improve cardiac remodeling of experimental autoimmune myocarditis rats. It also effectively improved the degree of myocardial fibrosis, which is related to the mechanism of regulation of TGF-β1 CTGF.

The neuropeptide cortistatin attenuates experimental autoimmune myocarditis via inhibition of cardiomyogenic T cell‐driven inflammatory responses

PubMed Central

Delgado‐Maroto, Virginia; Falo, Clara P; Forte‐Lago, Irene; Adan, Norma; Morell, Maria; Maganto‐Garcia, Elena; Robledo, Gema; O'Valle, Francisco; Lichtman, Andrew H; Gonzalez‐Rey, Elena

2017-01-01

Background and purpose Myocarditis is an inflammatory and autoimmune cardiovascular disease that causes dilated myocardiopathy and is responsible for high morbidity and mortality worldwide. Cortistatin is a neuropeptide produced by neurons and cells of the immune and vascular systems. Besides its action in locomotor activity and sleep, cortistatin inhibits inflammation in different experimental models of autoimmune diseases. However, its role in inflammatory cardiovascular disorders is unexplored. Here, we investigated the therapeutic effects of cortistatin in a well‐established preclinical model of experimental autoimmune myocarditis (EAM). Experimental Approach We induced EAM by immunization with a fragment of cardiac myosin in susceptible Balb/c mice. Cortistatin was administered i.p. starting 7, 11 or 15 days after EAM induction. At day 21, we evaluated heart hypertrophy, myocardial injury, cardiac inflammatory infiltration and levels of serum and cardiac inflammatory cytokines, cortistatin and autoantibodies. We determined proliferation and cytokine production by heart draining lymph node cells in response to cardiac myosin restimulation. Key Results Systemic injection of cortistatin during the effector phase of the disease significantly reduced its prevalence and signs of heart hypertrophy and injury (decreased the levels of brain natriuretic peptide) and impaired myocardial inflammatory cell infiltration. This effect was accompanied by a reduction in self‐antigen‐specific T‐cell responses in lymph nodes and in the levels of cardiomyogenic antibodies and inflammatory cytokines in serum and myocardium. Finally, we found a positive correlation between cardiac and systemic cortistatin levels and EAM severity. Conclusions and Implications Cortistatin emerges as a new candidate to treat inflammatory dilated cardiomyopathy. PMID:27922195

The Novel Extracellular Cyclophilin A (CyPA) - Inhibitor MM284 Reduces Myocardial Inflammation and Remodeling in a Mouse Model of Troponin I -Induced Myocarditis.

PubMed

Heinzmann, David; Bangert, Anna; Müller, Anna-Maria; von Ungern-Sternberg, Saskia N I; Emschermann, Frederic; Schönberger, Tanja; Chatterjee, Madhumita; Mack, Andreas F; Klingel, Karin; Kandolf, Reinhard; Malesevic, Miroslav; Borst, Oliver; Gawaz, Meinrad; Langer, Harald F; Katus, Hugo; Fischer, Gunter; May, Andreas E; Kaya, Ziya; Seizer, Peter

2015-01-01

Cyclophilins are a group of highly conserved cytosolic enzymes that have a peptidylprolyl cis/trans isomerase activity. Cyclophilin A (CyPA) can be secreted in the extracellular space by inflammatory cells and upon cell death. The presence of CyPA in patients with non-ischemic cardiomyopathy is associated with poor clinical prognosis. Here, we investigated the inhibition of extracellular CyPA in a mouse model of troponin I-induced autoimmune myocarditis using the strictly extracellular CyPA-inhibitor MM284. Since A/J mice develop severe inflammation and fibrosis after immunization with murine cardiac troponin I (mcTn I), we used this model to analyze the effects of an extracellular CyPA inhibition. As extracellular CyPA-inhibitor we used the recently described CsA-derivate MM284. In vitro studies confirmed that MM284 inhibits CyPA-induced monocytic migration and adhesion. A/J mice immunized with mcTnI were treated with MM284 or vehicle every second day. After 28 days, we found a considerable reduction of myocardial injury and fibrosis. Further analysis revealed a reduced myocardial presence of T-cells and macrophages compared to control treated animals. Whereas MMP-9 expression was reduced significantly by MM284, we observed no significant reduction of inflammatory cytokines such as IL-6 or TNFα. Extracellular CyPA plays an important role in autoimmune myocarditis for myocardial damage and fibrosis. Our data suggest a new pharmacological approach for the treatment of myocardial inflammation and reduction of cardiac fibrosis by inhibition of extracellular CyPA.

[Myocardial bridge as the only cause of acute coronary syndrome among the young patients].

PubMed

Miakinkova, Liudmila O; Teslenko, Yurii V; Tsyhanenko, Irina V

2018-01-01

Introduction: Myocardial bridge is an inborn anomaly of coronary artery development, when a part of it is submerged in a myocard, which is pressing the coronary artery to a systola and restrains coronary blood circulation. Generally this feature of coronary blood circulation does not cause any clinical symptoms because the 85% of coronary blood stream of the left ventricle is provided by diastolic filling. Hemodynamic changes in atherosclerosis, tahicardie, hypertrophie of myocard are leading to the manifestation of clinical symptoms of ischemia. The aim: The purpose of the investigation was to discover the features of clinical development of acute coronary syndrome caused by myocardial bridge of young patients without the features of atherosclerotical harm of coronary arteries. Materials and methods: Eight causes of acute coronary syndrome among patients of 28±8,5 years with myocardial bridge which was revealed during coronary angiography, were investigated. Standardized examination and conservative treatment of patients was held, except for three who have got interventional therapy. Results: According to our investigation, myocardial bridge of all investigated patients was located in the middle of the third front interventricular branch of the left coronary artery. Causes of acute coronary syndrome manifestation were tahicardia, spasms of coronary artery, inducted by iatrogenic factors hypertrophie of myocard, hypertrophic cardiomyopatie. Connection between the manifestation of clinical symptoms and length of tunneled segment which did not depend on the level of systolic compres was discovered. The results of conservative and interventional treatment were analyzed. Conclusions: Myocardial bridge can be the cause of myocardial ischemia among patients without signs of coronary atherosclerosis with additional hemodynamic risk facts such as tahicardia, spasms of coronary artery, hypertrophie of myocard. Clinical symptomatology of the acute coronary syndrome is more often observed among patients who's myocsrdial bridge is located in the middle of the third front interventricular branch of the left coronary artery. This is caused by perpendicular location of muscle fibers to coronary artery that increases systolic compression. Diastolic function and blood filling of coronary artery can be improved due to the medication beta-blockers therapy of patients with symptomatic myocardial bridge. A higher risk of appearance of restenosis of the stent is possible due to interventional treatment of young patients with myocardial bridge without atherosclerosis of coronary arteries.

Halofuginone alleviates acute viral myocarditis in suckling BALB/c mice by inhibiting TGF-β1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Xiao-Hua; Fu, Jia; Sun, Da-Qing, E-mail: daqingsuncd@163.com

2016-04-29

Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young adolescents. This study explored the function of halofuginone (HF) in Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited higher survival rate, lower heart/body weight, and more decreased blood sugar concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)-17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels. The expressions of transforming growth factor(TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) p65/ tumor necrosis factor-α (TNF-α) proteins were decreased by HF as well. Finally,more » the overexpression of TGF-β1 counteracted the protection effect of HF in CVB3-treated suckling mice. In summary, our study suggests HF increases the survival of CVB3 suckling mice, reduces the Th17 cells and pro-inflammatory cytokine levels, and may through downregulation of the TGF-β1-mediated expression of NF-κB p65/TNF-α pathway proteins. These results offer a potential therapeutic strategy for the treatment of VMC. - Highlights: • Halofuginone (HF) increases the survival of suckling BALB/c mice infected with acute CVB3. • HF reduces the expression of Th17 cell markers (IL-17 and IL-23) and the number of CD4{sup +} IL17{sup +} cells. • Pro-inflammatory cytokines levels associated with myocarditis were reduced by HF in CVB3-treated suckling mice. • HF alleviates VMC via inhibition of TGF-β1-mediated NF-κB p65/TNF-α pathway.« less

Infarct-like acute myocarditis: relation between electrocardiographic findings and myocardial damage as assessed by cardiac magnetic resonance imaging.

PubMed

Nucifora, Gaetano; Miani, Daniela; Di Chiara, Antonio; Piccoli, Gianluca; Artico, Jessica; Puppato, Michela; Slavich, Gianaugusto; De Biasio, Marzia; Gasparini, Daniele; Proclemer, Alessandro

2013-03-01

Acute myocarditis (AM) may occasionally have an infarct-like presentation. The aim of the present study was to investigate the relation between electrocardiographic (ECG) findings in this group of patients and myocardial damage assessed by cardiac magnetic resonance imaging (MRI) with the late gadolinium enhancement (LGE) technique. Myocardial damage may be associated with ECG changes in infarct-like AM. Forty-one consecutive patients (36 males; mean age, 36 ± 12 years) with diagnosis of AM according to cardiac MRI Lake Louise criteria and infarct-like presentation were included. The relation between site of ST-segment elevation (STE), sum of STE (sumSTE), time to normalization of STE, and development of negative T wave with the extent of LGE (expressed as % of left ventricular mass [%LV LGE]), was evaluated. Most (80%) patients presented with inferolateral STE; mean sumSTE was 5 ± 3 mm. Normalization of STE occurred within 24 hours in 20 (49%) patients. Development of negative T wave occurred in 28 (68%) patients. Cardiac MRI showed LGE in all patients; mean %LV LGE was 9.6 ± 7.2%. Topographic agreement between site of STE and LGE was 68%. At multivariate analysis, sumSTE (β = 0.42, P < 0.001), normalization of STE >24 hours (β = 0.39, P < 0.001), and development of negative T wave (β = 0.49, P < 0.001) were independently related to %LV LGE. Analysis of the site of STE underestimates the extent of myocardial injury among patients with infarct-like myocarditis. However, some ECG features (ie, sumSTE, normalization of STE >24 hours, and development of negative T wave) may help to identify patients with larger areas of myocardial damage. © 2012 Wiley Periodicals, Inc.

EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases

PubMed Central

Mao, Qunying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

2016-01-01

Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases. PMID:27436364

Effects of 1, 25-Dihydroxyvitamin D3 on Experimental Autoimmune Myocarditis in Mice.

PubMed

Hu, Fen; Yan, Lianhua; Lu, Shuai; Ma, Wenhan; Wang, Ya; Wei, Yuzhen; Yan, Xiaofei; Zhao, Xin; Chen, Zhijian; Wang, Zhaohui; Cheng, Bo

2016-01-01

Myocarditis is an important inflammatory disease of the heart which causes life-threatening conditions. 1, 25(OH)2 D3 has effects on multiple systems and diseases. The present study was aimed to investigate the effect of 1, 25(OH)2 D3 on experimental autoimmune myocarditis (EAM), and explored the underlying mechanisms involved. EAM was induced by immunizing BALB/c mice with cardiac α-myosin heavy chain peptides (MyHC-α). 1, 25(OH)2 D3 (1,000 ng/kg once) or vehicle was administered intraperitoneally every other day during the entire experiment. On day 21, transthoracic echocardiography was performed and cardiac inflammatory infiltration was detected by hematoxylin and eosin (HE). The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, and Western blots for the expression of protein caspase-3 and cleaved-caspase3 were used to evaluate apoptosis. Transmission electron microscopy and Western blots for the expression of protein Beclin-1, LC3B, and P62 were used to evaluate autophagy. The ratio of heart weight/body weight was significantly reduced in 1, 25(OH)2 D3 -treated EAM mice, compared with vehicle -treated ones. 1, 25(OH)2 D3 treatment improved cardiac function, diminished cell infiltration in cardiac, suppressed myocardial apoptosis, decreased the number of autophagosomes, and decreased the protein expression of Beclin-1, LC3-II and p62. The present results demonstrated that administration of 1, 25(OH)2 D3 decreased EAM severity. 1, 25(OH)2 D3 treatment may be a feasible therapeutic approach for EAM. © 2016 The Author(s) Published by S. Karger AG, Basel.

Cardiac involvement in ANCA (+) and ANCA (-) Churg-Strauss syndrome evaluated by cardiovascular magnetic resonance.

PubMed

Mavrogeni, Sophie; Karabela, Georgia; Gialafos, Elias; Stavropoulos, Efthymios; Spiliotis, George; Katsifis, Gikas; Kolovou, Genovefa

2013-10-01

The cardiovascular magnetic resonance (CMR) pattern of Churg-Strauss syndrome (CSS) includes myopericarditis, diffuse subendocardial vasculitis or myocardial infarction with or without cardiac symptoms and is usually associated with lack of antineutrophil cytoplasmic antibodies (ANCA). To correlate the CMR pattern with ANCA in CSS, compare it with healthy controls and systemic lupus erythematosus (SLE) patients and re-evaluate 2 yrs after the first CMR. 28 consecutive CSS, aged 42±7 yrs, were referred for CMR and 2 yrs re-evaluation. The CMR included left ventricular ejection fraction (LVEF), T2-weighted (T2-W), early (EGE) and late gadolinium enhanced (LGE) imaging. Their results were compared with 28 systemic lupus erythematosus (SLE) under remission and 28 controls with normal myocardial perfusion, assessed by scintigraphy. CMR revealed acute cardiac lesions in all ANCA (-) CSS with active disease and acute cardiac symptoms and only in one asymptomatic ANCA (+) CSS, with active disease. Diffuse subendocardial fibrosis (DSF) or past myocarditis was identified in both ANCA(+) and ANCA (-) CSS, but with higher incidence and fibrosis amount in ANCA (-) CSS (p<0.05). In comparison to SLE, both ANCA (+) and ANCA (-) CSS had higher incidence of DSF, lower incidence of myocarditis and no evidence of myocardial infarction, due to coronary artery disease (p<0.05). In 2 yrs CMR follow up, 1/3 of CSS with DSF presented LV function deterioration and one died, although immunosuppressive treatment was given early after CSS diagnosis. Cardiac involvement either as DSF or myocarditis, can be detected in both ANCA (+) and ANCA (-) CSS, although more clinically overt in ANCA (-). DSF carries an ominous prognosis for LV function. CMR, due to its capability to detect disease severity, before cardiac dysfunction takes place, is an excellent tool for CSS risk stratification and treatment individualization.

Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats.

PubMed

Okuda, Keiji; Fu, Hai Ying; Matsuzaki, Takashi; Araki, Ryo; Tsuchida, Shota; Thanikachalam, Punniyakoti V; Fukuta, Tatsuya; Asai, Tomohiro; Yamato, Masaki; Sanada, Shoji; Asanuma, Hiroshi; Asano, Yoshihiro; Asakura, Masanori; Hanawa, Haruo; Hao, Hiroyuki; Oku, Naoto; Takashima, Seiji; Kitakaze, Masafumi; Sakata, Yasushi; Minamino, Tetsuo

2016-01-01

Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.

Regulatory T cells protect mice against coxsackievirus-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway.

PubMed

Shi, Yu; Fukuoka, Masahiro; Li, Guohua; Liu, Youan; Chen, Manyin; Konviser, Michael; Chen, Xin; Opavsky, Mary Anne; Liu, Peter P

2010-06-22

Coxsackievirus B3 infection is an excellent model of human myocarditis and dilated cardiomyopathy. Cardiac injury is caused either by a direct cytopathic effect of the virus or through immune-mediated mechanisms. Regulatory T cells (Tregs) play an important role in the negative modulation of host immune responses and set the threshold of autoimmune activation. This study was designed to test the protective effects of Tregs and to determine the underlying mechanisms. Carboxyfluorescein diacetate succinimidyl ester-labeled Tregs or naïve CD4(+) T cells were injected intravenously once every 2 weeks 3 times into mice. The mice were then challenged with intraperitoneal coxsackievirus B3 immediately after the last cell transfer. Transfer of Tregs showed higher survival rates than transfer of CD4(+) T cells (P=0.0136) but not compared with the PBS injection group (P=0.0589). Interestingly, Tregs also significantly decreased virus titers and inflammatory scores in the heart. Transforming growth factor-beta and phosphorylated AKT were upregulated in Tregs-transferred mice and coxsackie-adenovirus receptor expression was decreased in the heart compared with control groups. Transforming growth factor-beta decreased coxsackie-adenovirus receptor expression and inhibited coxsackievirus B3 infection in HL-1 cells and neonatal cardiac myocytes. Splenocytes collected from Treg-, CD4(+) T-cell-, and PBS-treated mice proliferated equally when stimulated with heat-inactivated virus, whereas in the Treg group, the proliferation rate was reduced significantly when stimulated with noninfected heart tissue homogenate. Adoptive transfer of Tregs protected mice from coxsackievirus B3-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway and thus suppresses the immune response to cardiac tissue, maintaining the antiviral immune response.

EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases.

PubMed

Mao, Qunying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

2016-07-20

Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases.

Effect and Mechanism of QiShenYiQi Pill on Experimental Autoimmune Myocarditis Rats

PubMed Central

Lv, Shichao; Wu, Meifang; Li, Meng; Wang, Qiang; Xu, Ling; Wang, Xiaojing; Zhang, Junping

2016-01-01

Background To observe the effect of QiShenYiQi pill (QSYQ) on experimental autoimmune myocarditis rats, and to explore its mechanism of action. Material/methods Lewis rats underwent the injection of myocardial myosin mixed with Freund’s complete adjuvant were randomized into 3 groups: model, valsartan, and QSYQ groups. Rats injected with phosphate-buffered saline (PBS) mixed with Freund’s complete adjuvant were used as the control group. Rats were euthanized at 4 and 8 weeks, and we weighed rat body mass, heart mass, and left ventricular mass. Myocardium sections were stained with hematoxylin and eosin (H&E) and Masson trichrome. Myocardial TGF-β1 and CTGF protein expression was detected by immunohistochemistry, and myocardial TGF-β1 and CTGF mRNA expression was detected by real-time qPCR. Results QSYQ reduced HMI and LVMI, as well as the histological score of hearts and CVF, which further decreased over time, and its effect was significantly greater than that of valsartan at 4 and 8 weeks. After 4 weeks, QSYQ inhibited the protein and mRNA expression of TGF-β1 and CTGF, and its effect on lowering CTGF was significantly greater than that of valsartan. In addition, after 8 weeks, QSYQ also inhibited the protein and mRNA expression of CTGF, whereas there was no significant difference in the expression of myocardial TGF-β1. Conclusions This study provides evidence that QSYQ can improve cardiac remodeling of experimental autoimmune myocarditis rats. It also effectively improved the degree of myocardial fibrosis, which is related to the mechanism of regulation of TGF-β1 CTGF. PMID:26946470

Inhibition of Drp1 attenuates mitochondrial damage and myocardial injury in Coxsackievirus B3 induced myocarditis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Lin; Zhang, Ming; Yan, Rui

Viral myocarditis (VMC) is closely related to apoptosis, oxidative stress, innate immunity, and energy metabolism, which are all linked to mitochondrial dysfunction. A close nexus between mitochondrial dynamics and cardiovascular disease with mitochondrial dysfunction has been deeply researched, but there is still no relevant report in viral myocarditis. In this study, we aimed to explore the role of Dynamin-related protein 1 (Drp1)-linked mitochondrial fission in VMC. Mice were inoculated with the Coxsackievirus B3 (CVB3) and treated with mdivi1 (a Drp1 inhibitor). Protein expression of Drp1 was increased in mitochondria while decreased in cytoplasm and accompanied by excessive mitochondrial fission inmore » VMC mice. In addition, midivi1 treatment attenuate inflammatory cells infiltration in myocardium of the mice, serum Cardiac troponin I (CTnI) and Creatine kinase-MB (CK-MB) level. Mdivi1 also could improved the survival rate of mice and mitochondrial dysfunction reflected as the up-regulated mitochondrial marker enzymatic activities of succinate dehydrogenase (SDH), cytochrome c oxidase (COX) and mitochondrial membrane potential (MMP). At the same time, mdivi1 rescued the body weight loss, myocardial injury and apoptosis of cardiomyocyte. Furthermore, decease in LVEDs and increase in EF and FS were detected by echocardiogram, which indicated the improved myocardial function. Thus, Drp1-linked excessive mitochondrial fission contributed to VMC and midivi1 may be a potential therapeutic approach. - Highlights: • The expression of Drp1 is significantly increased in mitochondria while decreased in cytoplasm in VMC mice. • Drp1-linked excessive mitochondrial fission is involved in VMC. • Midivi1 treatment mitigate the mitochondrial damage, inflammation, apoptosis in VMC mice. • The disturbance of mitochondrial dynamics may be a new therapeutic target for VMC.« less

Treatment of inflammatory dilated cardiomyopathy and (peri)myocarditis with immunosuppression and i.v. immunoglobulins.

PubMed

Maisch, Bernhard; Hufnagel, Günther; Kölsch, Susanne; Funck, Rainer; Richter, Annette; Rupp, Heinz; Herzum, Matthias; Pankuweit, Sabine

2004-09-01

Treatment objectives in inflammatory dilated cardiomyopathy (DCMi), myocarditis (M) and peri(myo)carditis are 1) the elimination of inflammatory cells from the myocardium and pericardium, 2) the elimination or (second best) mitigation of B-cell products such as antibodies and immuncomplexes directed against cardiac epitopes such as sarcolemmal, fibrillary and mitochondrial epitopes, and 3) the eradication of the causative viral or microbial agent, if present. A "non-specific" anti-inflammatory treatment in peri(myo)carditis can be carried out with antiphlogistics (NSAIDs preferably colchicine 1-3 mg/d) independent from the presence of the infective agent. In larger virus and bacteria negative effusions we recommend intrapericardial instillation of cristalloid triamcinolon (Volon A) at a dose of 500 mg/m(2), which should be left in place to have a sustained effect over at least 4 weeks. This will effectively prevent recurrences particularly when colchicine is added over a period of at least 3-6 months. Taking into account the 2004 ESC task force recommendations on the management of pericardial diseases the treatment recommendation for NSAIDs and colchicine can be classified as level of evidence A, indication class I, for intrapericardial triamcinolon instillation as level of evidence B, indication class IIa. In (immuno)histologically validated autoreactive (virus negative) myocarditis and DCMi double-blind randomized trials are lacking to demonstrate the superiority of immunosuppression over conventional heart failure management. The only published randomized and double-blind immunosuppression treatment trial (American Myocarditis Treatment Trial) was underpowered and did not distinguish viral from non-viral disease. It showed neither benefit nor harm of a combination of cyclosporin and prednisone. A number of retrospective analyses of immunosuppression in myocarditis showed some benefit of surrogate parameters (ejection fraction, exercise tolerance) but improvement under conventional heart failure treatment cannot be ruled out completely as the main cause for amelioration. ESETCID (European Study on the Epidemiology and Treatment of Cardiac Inflammatory Disease) is a double-blind, randomized, placebo-controled three-armed trial with prednisolone and azathioprine for autoreactive (virus negative) DCMi, interferon alpha for enterovirus positive DCMi, high-dose immunoglobulin for cytomegalovirus and intermediate dose for adeno- and Parvo B19 DCMi. It has now randomized more than 120 patients to the different treatment arms. Its final result has still to be awaited.-Patients not willing to randomize in the trial were included in a registry follow-up, which shows improvement of hemodynamic parameters and elimination of the inflammation in the majority of patients. This is in concordance with several non-randomized trials. Since evidence is conflicting (level of evidence C, indication class IIb; if negative viral etiology is taken into consideration class IIa) treatment with immunosuppression cannot be generally recommended but should be further evaluated in doubleblind randomized clinical trials or at least in controlled trials and registries. This also applies to treatment with interferon for enteroviral or other viral infections in the heart. : The elimination of anticardiac antibodies, which have been associated with DCMi, is a currently discussed concept, which is supported by published registry data and a few very small controlled investigations but not by a randomized double-blind trial with clinical endpoints of relevance. In some studies immunoglobulins have been substituted, so that an additional immunomodulatory effect has to be taken into account. The current proof of concept can be ranked level of evidence C, indication class IIa only. An even more challenging and still more attractive hypothesis is that cardiac inflammation caused by specific circulating beta-adrenoceptor antibodies can be eradicated with the elimination of the beta-receptor antibody thus healing dilated cardiomyopathy. Application of this approach can be ranked level of evidence C, indication class IIb at present only. Therefore these two pathophysiologically attractive concepts have to await further validation by a double-blind, randomized clinical endpoint trial. It has been shown that immunoglobulins have both an antiviral and an anti-inflammatory effect. They may suppress proinflammatory cytokines and reduce oxidative stress. HIGH-DOSE I.V. In biopsy proven CMVmyocarditis a controlled trial demonstrated eradication of inflammation and of the virus (level of evidence B, indication class IIa), which is in accordance with registry data and case reports. In suspected myocarditis (not biopsy proven, no viral etiology established or excluded) conflicting data exist with respect to the improvement of surrogate markers such as the ejection fraction under high-dose immunoglobulins. More evidence can be weighted in favour of a positive treatment effect (level of evidence B, indication class IIb). Importantly there were no detrimental effects of the ivIG reported in these trials. One has to consider the high costs of this treatment, however. A trial taking into account the different etiologies (different viruses assessed separately vs. non-viral/autoreactive vs. placebo) is still lacking. MODERATE-DOSE I.V. Registry data support a positive effect of 20 g i.v. pentaglobin (IgG and IgM) in adenovirus positive myocarditis for clinical improvement, eradication of both the inflammation and the virus. In Parvo B19 myocarditis our own registry data indicate that clinical improvement can be noted, but only inflammation is successfully eliminated, whereas Parvo B19 persistence remains a problem in the majority of patients. In Parvo B19 associated DCMi therefore dose finding studies and randomized trials are needed.

Retrospective Surveillance of Wastewater To Examine Seasonal Dynamics of Enterovirus Infections

EPA Science Inventory

Enteroviruses are RNA viruses that are responsible for both mild gastroenteritis and mild respiratory illnesses as well as debilitating diseases such as meningitis and myocarditis. The disease burden of enteroviruses in the United States is difficult to assess because most infect...

Gene-targeted mice lacking the Trex1 (DNase III) 3'-->5' DNA exonuclease develop inflammatory myocarditis.

PubMed

Morita, Masashi; Stamp, Gordon; Robins, Peter; Dulic, Anna; Rosewell, Ian; Hrivnak, Geza; Daly, Graham; Lindahl, Tomas; Barnes, Deborah E

2004-08-01

TREX1, originally designated DNase III, was isolated as a major nuclear DNA-specific 3'-->5' exonuclease that is widely distributed in both proliferating and nonproliferating mammalian tissues. The cognate cDNA shows homology to the editing subunit of the Escherichia coli replicative DNA polymerase III holoenzyme and encodes an exonuclease which was able to serve a DNA-editing function in vitro, promoting rejoining of a 3' mismatched residue in a reconstituted DNA base excision repair system. Here we report the generation of gene-targeted Trex1(-/-) mice. The null mice are viable and do not show the increase in spontaneous mutation frequency or cancer incidence that would be predicted if Trex1 served an obligatory role of editing mismatched 3' termini generated during DNA repair or DNA replication in vivo. Unexpectedly, Trex1(-/-) mice exhibit a dramatically reduced survival and develop inflammatory myocarditis leading to progressive, often dilated, cardiomyopathy and circulatory failure.

[Effects of Chinese herbal compound for supplementing qi and activating blood circulation on actin, Cx43 expressions and gap junctional intercellular communication functions of myocardial cells in patients with Coxsackie virus B 3 viral myocarditis].

PubMed

Zhang, Ming-xue; He, Wei; Gu, Ping

2010-08-01

To observe the effect of Chinese herbal compound for supplementing qi and activating blood circulation (CHC) on the gap junctional intercellular communication (GJIC) function of myocardial cells in patients with Coxsackie virus B 3 (CVB3) viral myocarditis. Expressions of actin and connexin43 (Cx43) in myocardial cells of patients arranged in three groups (the normal control group, the viral infected group and the CHC treated group) were detected by immunohistochemical method; the fluorescence photobleaching recovery rate of cells was detected by laser scanning confocal microscope. As compared with the viral infected group, the expressions of actin and Cx43 were increased and the GJIC function was improved in the CHC treated group. CHC could antagonize viral injury on skeleton protein, and repair the structure of gap junction channel to improve the GJIC function of myocardial cells after being attacked by CVB3.

Type I Diabetes Mellitus: Genetic Factors and Presumptive Enteroviral Etiology or Protection

PubMed Central

Precechtelova, Jana; Borsanyiova, Maria; Sarmirova, Sona

2014-01-01

We review type 1 diabetes and host genetic components, as well as epigenetics and viruses associated with type 1 diabetes, with added emphasis on the enteroviruses, which are often associated with triggering the disease. Genus Enterovirus is classified into twelve species of which seven (Enterovirus A, Enterovirus B, Enterovirus C, and Enterovirus D and Rhinovirus A, Rhinovirus B, and Rhinovirus C) are human pathogens. These viruses are transmitted mainly by the fecal-oral route; they may also spread via the nasopharyngeal route. Enterovirus infections are highly prevalent, but these infections are usually subclinical or cause a mild flu-like illness. However, infections caused by enteroviruses can sometimes be serious, with manifestations of meningoencephalitis, paralysis, myocarditis, and in neonates a fulminant sepsis-like syndrome. These viruses are often implicated in chronic (inflammatory) diseases as chronic myocarditis, chronic pancreatitis, and type 1 diabetes. In this review we discuss the currently suggested mechanisms involved in the viral induction of type 1 diabetes. We recapitulate current basic knowledge and definitions. PMID:25574400

Crystals in brain and meninges in primary hyperoxaluria and oxalosis.

PubMed Central

Haqqani, M T

1977-01-01

A case of primary hyperoxaluria and oxalosis with chronic renal failure, crystalline myocarditis, and disseminated calcium oxalate crystal deposition in various tissues including the brain and meninges is described. Deposition of crystals in brain and meninges is exceptionally rare in primary oxalosis. Images PMID:838867

Genetic and antigenic characterization of Bungowannah virus, a novel pestivirus

USDA-ARS?s Scientific Manuscript database

Bungowannah virus, a possible new species of pestivirus, has been associated with a disease syndrome in pigs characterised by myocarditis with a high incidence of stillbirths. The current studies have identified the entire viral genome sequence, confirming the unique identity of this virus and sugge...

Symptomatic Acute Toxoplasmosis in Returning Travelers

PubMed Central

Henao-Martínez, Andrés F; Franco-Paredes, Carlos; Palestine, Alan G; Montoya, Jose G

2018-01-01

Abstract We report a family who acquired acute toxoplasmosis after a trip to Central America. One member developed severe clinical manifestations including bilateral chorioretinitis, hepatitis, and myocarditis requiring therapy. Symptomatic acute toxoplasmosis is unusual and possesses a diagnostic challenge. We discuss the clinical and epidemiological implications, laboratory diagnosis, and treatment plan. PMID:29644250

ACAM2000(TM): The New Smallpox Vaccine for United States Strategic National Stockpile

DTIC Science & Technology

2010-01-01

1963–1968. BMC Public Health. 2003;3:26. 36. Morgan J, Roper MH, Sperling L, et al. Myocarditis, pericarditis, and dilated cardiomyopathy after...51. von Landenberg P, Lehmann HW, Modrow S. Human parvovirus B19 infection and antiphospholipid antibodies. Autoimmun Rev. 2007;6(5):278–285. 52

[Adaptive reactions of students from mountain and plain regions of Latin America to conditions of middle Russia].

PubMed

Ermakova, N V

2003-01-01

This article contains results of the comparative study of the functional state of respiratory and cardiovascular systems of almost healthy students (man) of age 19-22, inhabitants of mountain and plain regions of Latin America during their adaptation to the conditions of middle Russia. We have established that there are reliable distinctions in the functional state of cardio-respiratory system of students from mountain and plain regions of Latin America. So for representatives of mountain regions of LA were typical higher indicators of vital capacity, permeability of large and medium bronchial tubes, stroke volume, lower indicators of heart rate, systolic arterial pressure, myocard tension index, but higher coefficient of myocard efficiency than for inhabitants the plain. Considerable distinctions have been observed also in the intercommunication between different indicators. There have been marked considerable correlation connections between small bronchial tubes permeability and cardiovascular system indicators for plain inhabitants. For mountain regions inhabitants almost every indicator of bronchial tubes permeability correlate reliably with vital capacity, but didn't correlate with hemodynamics indicators.

Isolation, molecular characterization, and phylogenetic analysis of encephalomyocarditis virus from South China tigers in China.

PubMed

Liu, Huimin; Yan, Qi; Zhao, Bo; Luo, Jing; Wang, Chengmin; Du, Yingchun; Yan, Jing; He, Hongxuan

2013-10-01

Although encephalomyocarditis virus (EMCV) can infect many host species and cause myocarditis and sudden death in many species, little is known about EMCV infection in tigers. A virus was isolated from organs of dead South China tigers with sudden death in southern China. The production of cytopathic effect on BHK cells, and the results of PCR, electron microscopy (EM), and whole genome sequencing indicated that the pathogen was EMCV, the strain was named FJ13. Other pathogenic agents were excluded as possible pathogenic agents. Phylogenetic analyses of the whole genome, ORF (open reading frame) and CCR (capsid coding region) using the neighbour-joining method revealed that EMCV isolates cluster into two groups (group 1 and 2) with two sub-clusters within group 1 (group 1a and 1b), and FJ13 belongs to group 1a. Animal experiment showed that the isolated strain FJ13 could cause clinical symptoms and pathological changes. The results of this study indicated that FJ13 caused myocarditis of tigers and provided new epidemiologic data on EMCV in China. Copyright © 2013 Elsevier B.V. All rights reserved.

Carvedilol has stronger anti-inflammation and anti-virus effects than metoprolol in murine model with coxsackievirus B3-induced viral myocarditis.

PubMed

Wang, Dan; Chen, Yiming; Jiang, Jianbin; Zhou, Aihua; Pan, Lulu; Chen, Qi; Qian, Yan; Chu, Maoping; Chen, Chao

2014-09-01

This study aims to compare the effects of carvedilol and metoprolol in alleviating viral myocarditis (VMC) induced by coxsackievirus B3 (CVB3) in mice. A total of 116 Balb/c mice were included in this study. Ninety-six mice were inoculated intraperitoneally with CVB3 to induce VMC. The CVB3 inoculated mice were evenly divided into myocarditis group (n=32), carvedilol group (n=32) and metoprolol group (n=32). Twenty mice (control group) were inoculated intraperitoneally with normal saline. Hematoxylin and eosin staining and histopathologic scoring were used to investigate the effects of carvedilol and metoprolol on myocardial histopathologic changes on days 3 and 5. In addition, serum cTn-I levels, cytokine levels and virus titers were determined using chemiluminescence immunoassay, enzyme-linked immunosorbent assay and plaque assay, respectively, on days 3 and 5. Finally, the levels of phosphorylated p38MAPK were studied using immunohistochemical staining and Western blotting on day 5. Carvedilol had a stronger effect than metoprolol in reducing the pathological scores of VMC induced by CVB3. Both carvedilol and metoprolol reduced the levels of cTn-I, but the effect of carvedilol was stronger. Carvedilol and metoprolol decreased the levels of myocardial pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokine, with the effects of carvedilol being stronger than those of metoprolol. Carvedilol had a stronger effect in reducing myocardial virus concentration compared with metoprolol. Carvedilol was stronger than metoprolol in decreasing the levels of myocardial phosphorylated p38MAPK. In conclusion, carvedilol was more potent than metoprolol in ameliorating myocardial lesions in VMC, probably due to its stronger modulation of the balance between pro- and anti-inflammatory cytokines by inhibiting the activation of p38MAPK pathway through β1- and β2-adrenoreceptors. Copyright © 2014 Elsevier B.V. All rights reserved.

Construction of a subgenomic CV-B3 replicon expressing emerald green fluorescent protein to assess viral replication of a cardiotropic enterovirus strain in cultured human cells.

PubMed

Wehbe, Michel; Huguenin, Antoine; Leveque, Nicolas; Semler, Bert L; Hamze, Monzer; Andreoletti, Laurent; Bouin, Alexis

2016-04-01

Coxsackieviruses B (CV-B) (Picornaviridae) are a common infectious cause of acute myocarditis in children and young adults, a disease, which is a precursor to 10-20% of chronic myocarditis and dilated cardiomyopathy (DCM) cases. The mechanisms involved in the disease progression from acute to chronic myocarditis phase and toward the DCM clinical stage are not fully understood but are influenced by both viral and host factors. Subgenomic replicons of CV-B can be used to assess viral replication mechanisms in human cardiac cells and evaluate the effects of potential antiviral drugs on viral replication activities. Our objectives were to generate a reporter replicon from a cardiotropic prototype CV-B3/28 strain and to characterize its replication properties into human cardiac primary cells. To obtain this replicon, a cDNA plasmid containing the full CV-B3/28 genome flanked by a hammerhead ribozyme sequence and an MluI restriction site was generated and used as a platform for the insertion of sequences encoding emerald green fluorescent protein (EmGFP) in place of those encoding VP3. In vitro transcribed RNA from this plasmid was transfected into HeLa cells and human primary cardiac cells and was able to produce EmGFP and VP1-containing polypeptides. Moreover, non-structural protein biological activity was assessed by the specific cleavage of eIF4G1 by viral 2A(pro). Viral RNA replication was indirectly demonstrated by inhibition assays, fluoxetine was added to cell culture and prevented the EmGFP synthesis. Our results indicated that the EmGFP CV-B3 replicon was able to replicate and translate as well as the CV-B3/28 prototype strain. Our EmGFP CV-B3 replicon will be a valuable tool to readily investigate CV-B3 replication activities in human target cell models. Copyright © 2016 Elsevier B.V. All rights reserved.

Myopericarditis in acquired immunodeficiency syndrome diagnosed by gallium scintigraphy.

PubMed Central

Cregler, L. L.; Sosa, I.; Ducey, S.; Abbey, L.

1990-01-01

Myocarditis is among the cardiac complications of acquired immunodeficiency syndrome and, yet, is often not discovered until autopsy. Gallium scintigraphy has been employed in diagnosing this entity, but few data are available about its diagnostic accuracy and value. Here, the authors report two cases of myopericarditis as diagnosed by gallium scan. Images Figure 1 Figure 2 PMID:2398508

The pathogenesis of foot-and-mouth disease II; viral pathways in swine, small ruminants, and wildlife, myotropism, chronic syndromes, and molecular virus-host interactions

USDA-ARS?s Scientific Manuscript database

Investigation of the pathogenesis of foot-and-mouth disease (FMD) has focused on study of the disease in cattle with less emphasis on pigs, small ruminants, and wildlife. “Atypical” FMD-associated syndromes such as myocarditis, reproductive losses, and chronic heat-intolerance have also received lit...

Lupus myocarditis: case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaManna, M.M.; Lumia, F.J.; Gordon, C.I.

1988-03-01

Although gallium-67 (/sup 67/Ga) accumulates in both neoplastic and inflammatory tissues, indium-111 (/sup 111/In) labeled leukocytes are seen only in inflammatory cells. Indium-111-labeled leukocytes therefore are a useful agent in the noninvasive differentiation of inflammatory tissue from neoplastic tissue. This case is an interesting example of the use of /sup 111/In-labeled leukocytes to make that differentiation.

Comparison of Clinical Presentation of Acute Myocarditis Following Smallpox Vaccination to Acute Coronary Syndromes in Patients 40 Years of Age

DTIC Science & Technology

2005-05-15

539–543. 4. Kuhl U, Pauschinger M, Bock T, Klingel K, Schwimmbeck CP, Seeberg B, Krautwurm L, Poller W, Schultheiss HP, Kandolf R. Parvovirus B19 ... parvoviruses and have been unrelated to vaccinations.2–4 It is unknown whether the presentations of those patients would be substantially different from

Pertussis-like syndrome associated with adenovirus presenting with hyperleukocytosis: Case report

PubMed Central

Sarbay, Hakan; Polat, Aziz; Mete, Emin; Balci, Yasemin Isik; Akin, Mehmet

2016-01-01

Adenovirus is an infectious viral agent that causes variety of clinical presentations such as respiratory disease, conjunctivitis, and gastroenteritis. Hepatitis, pancreatitis, myocarditis, encephalitis, and disseminated infection are primarily seen in immunocompromised patients. Rarely, adenovirus infection can present with pertussis-like syndrome. Described here is case of pertussis-like syndrome associated with adenovirus presenting with hyperleukocytosis. PMID:28058402

Epstein-Barr virus myocarditis as the first symptom of infectious mononucleosis.

PubMed

Zabala López, Sergio; Vicario, Juana M; Lerín, Francisco J; Fernández, Amalia; Pérez, Gloria; Fonseca, Cherpentier

2010-01-01

This case report describes a 20-year-old immunocompetent man with an episode of chest pain radiating into both arms, an increase in the level of myocardial enzymes, electrocardiogram abnormalities (widespread ST-segment elevation and q waves in leads V(4)-V(6)) and serological evidence for acute Epstein-Barr Virus infection preceding typical signs and symptoms of infectious mononucleosis.

[A case of lupus myocarditis and nephritis with transient foramen jugular syndrome].

PubMed

Kohro-Kawata, J; Nakamura, H; Yamamoto, T; Fukuta, S; Matsuzaki, M

1997-10-01

A 46-year-old man was admitted to our clinic because of acute heart failure. Six years before admission he was pointed out cardiomegary and hematuria. One year later, he was diagnosed as having jugular foramen syndrome. On admission, he had a fever and dyspnea. Pansystolic blowing murmur was audible at the apex. The chest ratio on his chest X-ray was 52.5%. An electrocardiogram showed left ventricular hypertrophy. An echocardiogram showed marked dilatation and severe dysfunction of left ventricle. Radionuclide scanning with technetium 99 m pyrophosphate identified inflammatory change in the apex. Myocardial biopsy showed fibrotic degeneration and IgG deposits in myocardium. Blood examination showed anemia, lymphopenia. positive anti-nuclear antibody (1000 times, shaggy pattern), positive anti ds-DNA antibody and hypocomplementemia. Furthermore, proteinuria was pointed out. Renal biopsy showed focal segmental glomerulonephritis with active necrotizing lesion (type III nephritis). Lupus myocarditis and nephritis was diagnosed. After prednisolone (80 mg/day) was administered. left ventricular function and hypocomplementemia improved. The ACE inhibitor was also used for proteinuria. In spite of a little amount of blood transfusion, he showed hepatic hemosiderosis. We suspect that the cause of hemosiderosis was related chronic inflammation of active lupus. It was treated with Erythropoietin.

The immunoproteasome-specific inhibitor ONX 0914 reverses susceptibility to acute viral myocarditis.

PubMed

Althof, Nadine; Goetzke, Carl Christoph; Kespohl, Meike; Voss, Karolin; Heuser, Arnd; Pinkert, Sandra; Kaya, Ziya; Klingel, Karin; Beling, Antje

2018-02-01

Severe heart pathology upon virus infection is closely associated with the immunological equipment of the host. Since there is no specific treatment available, current research focuses on identifying new drug targets to positively modulate predisposing immune factors. Utilizing a murine model with high susceptibility to coxsackievirus B3-induced myocarditis, this study describes ONX 0914-an immunoproteasome-specific inhibitor-as highly protective during severe heart disease. Represented by reduced heart infiltration of monocytes/macrophages and diminished organ damage, ONX 0914 treatment reversed fulminant pathology. Virus-induced immune response features like overwhelming pro-inflammatory cytokine and chemokine production as well as a progressive loss of lymphocytes all being reminiscent of a sepsis-like disease course were prevented by ONX 0914. Although the viral burden was only minimally affected in highly susceptible mice, resulting maintenance of immune homeostasis improved the cardiac output, and saved animals from severe illness as well as high mortality. Altogether, this could make ONX 0914 a potent drug for the treatment of severe virus-mediated inflammation of the heart and might rank immunoproteasome inhibitors among drugs for preventing pathogen-induced immunopathology. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Délais de prise en charge des syndromes coronariens aigus avec sus-décalage du segment ST à Ouagadougou et facteurs associés à un allongement de ces délais: étude transversale à propos de 43 cas colligés au CHU-Yalgado Ouédraogo

PubMed Central

Yameogo, Nobila Valentin; Samadoulougou, André; Millogo, Georges; Kologo, Koudougou Jonas; Kombassere, Karim; Toguyeni, Boubacar Jean Yves; Zabsonre, Patrice

2012-01-01

La prise en charge de l'infarctus du myocarde est une course contre la montre et les trois premières heures constituent les « golden hours ». Les objectifs de ce travail étaient de déterminer le délai de prise en charge des infarctus du myocarde du myocarde au Burkina Faso, les facteurs liés à un allongement du délai et le pronostic des patients. Il s'agit d'une étude transversale descriptive menée de Septembre 2010 à Août 2011. Le critère d'inclusion était l'infarctus du myocarde dont le diagnostic était basé sur des critères clinique (douleur angineuse), électrocardiographique (sus-décalage persistant du segment ST dans au moins deux dérivations contiguës du même territoire coronaire, onde Q de nécrose) et biologique (élévation de la troponine). Les informations relatives au délai de prise en charge ont été recueillies: début du premier symptôme, contact avec le premier agent de santé et le cardiologue, nombre de centre de santé consulté avant le transfert en cardiologie, situation géographique des patients, moyen de transport utilisé. Les données ont été analysées grâce au logiciel SPSS version 17. Durant la période d’étude, 43 patients d’âge moyen de 56,51 ± 12,91 ans ont été admis pour infarctus du myocarde. Plus de la moitié des patients (72,0%) habitait Ouagadougou et sa banlieue. Le délai moyen entre le début de la douleur et la consultation dans la première structure sanitaire était de 48 ± 20,8 heures; celui entre le début de la douleur et la réalisation du premier ECG était en moyenne de 8,6 ±4,5 jours. Le délai entre la réalisation de l'ECG et l'admission dans le service de cardiologie était de 4,35 ±4,0 jours [00 heure et 13 jours]. Le délai entre l'admission dans le service de cardiologie et la thrombolyse était de 34 minutes. Enfin le délai entre le début de la douleur et le contact avec le cardiologue était de 9,6±3,5 jours. Il n'y avait pas de différence statiquement significative (P = 0,076) entre le délai de consultation des malades résidant en campagne et ceux résidant en ville. Le moyen de déplacement le plus utilisé était les transports en commun (67,4%). Aucun patient n’était référé par un transport médicalisé. Aucun patient n’était référé après la première consultation dans une structure sanitaire. Seuls 6 patients étaient référés avec le diagnostic de SCA ST+. L’âge de plus de 60 ans (P = 0,016), la prescription des antalgiques (p =0,021) et le niveau socioéconomique faible (P= 0,038) étaient également des facteurs associés à un allongement des délais de prise en charge. La reperfusion myocardique était constituée par la thrombolyse à la streptokinase qui a été réalisée chez 2 patients. La coronarographie n'a pas été réalisée. L’évolution a été marquée par 5 décès (11,6%). la prise en charge des infarctus du myocarde au Burkina Faso est caractérisée par de très longs délais. Elle n'est de ce fait pas optimale. PMID:23396976

Subchronic Studies of Chlorotrifluorethylene

DTIC Science & Technology

1989-06-01

colonic nematodiasis, focal myocarditis, renal retention cysts , pulmonary subpl.ural histiocytosis, focal dacryoadenitis, rhinitis, and multifocal...compared to controls (pɘ.01). Among female rats, te incidences of grossly detected paraovarian cysts were 40, 10, 10, and 0% in the cr,-trol, 0.25, 0.5...level. The histopathologic examination also confirmed each paraovarian cyst in female rats and also revealed paraovarian cysts that ,v-re not grossly

M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

PubMed

Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

2014-07-31

Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cardiac magnetic resonance in myocardial disease.

PubMed

Sechtem, U; Mahrholdt, H; Vogelsberg, H

2007-12-01

For a number of patients it is difficult to diagnose the cause of cardiac disease. In such patients cardiac magnetic resonance is useful for helping to make a differential diagnosis between ischaemic and dilated cardiomyopathy; identifying patients with myocarditis; diagnosing cardiac involvement in sarcoidosis and Chagas' disease; identifying patients with unusual forms of hypertrophic cardiomyopathy and those with continuing myocardial damage; and defining the sequelae of ablation treatment for hypertrophic obstructive cardiomyopathy.

Tc-99m pyrophosphate myocardial scanning in Chagas' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

1981-04-01

Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

Tc-99m pyrophosphate myocardial scanning in Chagas' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goncalves da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

1981-04-01

Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas's disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

Response of refractory Kawasaki disease to pulse steroid and cyclosporin A therapy.

PubMed

Raman, V; Kim, J; Sharkey, A; Chatila, T

2001-06-01

We describe a child with aggressive and protracted Kawasaki disease with coronary aneurysms, myocarditis, pericarditis and valvular insufficiency, despite repeated administration of intravenous immunoglobulin. After a transient response to pulse corticosteroids, his disease ultimately subsided with combination therapy with pulse and high dosage corticosteroids and cyclosporin A. Aggressive immunosuppressive therapy with high dosage corticosteroids and cyclosporin A may be beneficial in patients with refractory Kawasaki disease.

Learning from myocarditis: mimicry, chaos and black holes

PubMed Central

Rose, Noel R.

2014-01-01

Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes of heart failure, especially in children and young adults. We have developed animal models to investigate their pathogenesis by infecting genetically susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin or its immunodominant peptide. A number of valuable lessons have emerged from our study of this paradigm of an infection-induced autoimmune disease. We understand more clearly how natural autoimmunity, as an important component of normal physiology, must be recalibrated regularly due to changes caused by infection or other internal and external stimuli. A new normal homeostatic platform will be established based on its evolutionary fitness. A loss of homeostasis with out-of-control normal autoimmunity leads to autoimmune disease. It is signified early on by a spread of an adaptive autoimmune response to novel epitopes and neighboring antigens. The progression from infection to normal, well-balanced autoimmunity to autoimmune disease and on to irreversible damage is a complex, step-wise process. Yet, chaos theory provides hope that the pattern is potentially predictable. Infection-induced autoimmune disease represents a sequence of events heading for a train wreck at the end of the line. Our aim in autoimmune disease research must be to stop the train before this happens. PMID:24904749

Learning from myocarditis: mimicry, chaos and black holes.

PubMed

Rose, Noel R

2014-01-01

Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes of heart failure, especially in children and young adults. We have developed animal models to investigate their pathogenesis by infecting genetically susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin or its immunodominant peptide. A number of valuable lessons have emerged from our study of this paradigm of an infection-induced autoimmune disease. We understand more clearly how natural autoimmunity, as an important component of normal physiology, must be recalibrated regularly due to changes caused by infection or other internal and external stimuli. A new normal homeostatic platform will be established based on its evolutionary fitness. A loss of homeostasis with out-of-control normal autoimmunity leads to autoimmune disease. It is signified early on by a spread of an adaptive autoimmune response to novel epitopes and neighboring antigens. The progression from infection to normal, well-balanced autoimmunity to autoimmune disease and on to irreversible damage is a complex, step-wise process. Yet, chaos theory provides hope that the pattern is potentially predictable. Infection-induced autoimmune disease represents a sequence of events heading for a train wreck at the end of the line. Our aim in autoimmune disease research must be to stop the train before this happens.

Levitronix bilateral ventricular assist device, a bridge to recovery in a patient with acute fulminant myocarditis and concomitant cerebellar infarction.

PubMed

Huang, Yi-Fan; Hsu, Po-Shun; Tsai, Chien-Sung; Tsai, Yi-Ting; Lin, Chih-Yuan; Ke, Hong-Yan; Lin, Yi-Chang; Yang, Hsiang-Yu

2018-02-07

We report on the case of a 27-year-old male who presented to our emergency room with chest tightness, dyspnoea and cold sweats. The 12-lead electrocardiogram showed diffuse ventricular tachycardia with wide QRS complexes. Troponin-I level was elevated to 100 ng/ml. The coronary angiogram showed good patency of all three coronary vessels, and acute fulminant myocarditis was suspected. The patient underwent cardiopulmonary resuscitation in the catheter room and high-dose inotropic support was initiated to stabilise his haemodynamic status. After resuscitation, the patient was in a coma and acute stroke was highly suspected. In addition, deteriorating cardiogenic shock with acute renal failure and pulmonary oedema were also detected. Due to haemodynamic compromise despite high-dose inotropic support, a Levitronix ® bilateral ventricular assist device (Bi-VAD) was implanted on an emergency basis for circulatory support. Postoperative brain computed tomography revealed acute left cerebellar infarction. Because the patient had left cerebellar infarction with right hemiplegia, heart transplantation was contraindicated. Eventually, cardiac systolic function recovered well and the patient underwent successful Bi-VAD removal after a total of 18 days on Levitronix ® haemodynamic support. He was weaned from the ventilator two weeks later and was discharged 10 days later.

Anti-mitochondrial flavoprotein autoantibodies of patients with myocarditis and dilated cardiomyopathy (anti-M7): interaction with flavin-carrying proteins, effect of vitamin B2 and epitope mapping

PubMed Central

Stähle, I; Brizzio, C; Barile, M; Brandsch, R

1999-01-01

Vitamin B2 and flavin cofactors are transported tightly bound to immunoglobulin in human serum. We reasoned that anti-mitochondrial flavoprotein autoantibodies (αFp-AB) present in the serum of patients with myocarditis and cardiomyopathy of unknown aetiology may form immunoglobulin aggregates with these serum proteins. However, immunodiffusion and Western blot assays demonstrated that the flavin-carrying proteins were not recognized by αFp-AB. Apparently the flavin moiety in the native protein conformation was inaccessible to αFp-AB. This conclusion was supported by the absence of an immunoreaction between the riboflavin-binding protein from egg white and αFP-AB. Intravenous application of vitamin B2 to rabbits immunized with 6-hydroxy-d-nicotine oxidase, a bacterial protein carrying covalently attached FAD, did not neutralize αFp-AB which had been raised in the serum of the animals. FAD-carrying peptides generated from 6-hydroxy-d-nicotine oxidase by trypsin and chymotrypsin treatment were not recognized by the αFp-AB, but those generated by endopeptidase Lys were. This demonstrates that the epitope recognized by αFp-AB comprises, besides the flavin moiety, protein secondary structure elements. PMID:10193410

Giant cell myocarditis with cardiac tamponade: a rare combination.

PubMed

Murty, O P

2008-09-01

Giant cell myocarditis (GCM) is a rare but fatal disease of idiopathic origin. It results in focal necrosis of myocardium. This is a case report of middle aged Malaysian Indian female who died due to cardiac tamponade due to rupture myocardium and tear in the root of aorta. On naked eye examination, it simply resembled as recent as well as old fibrotic areas of myocardial infarction. She was clinically diagnosed as a case of obstructive cardiomyopathy with atrioventricular block, and was on pace maker. There was subendocardial fibrosis and left ventricular transmural infarction in the left ventricle. On histopathology, this was diagnosed as GCM, there were widespread areas of inflammatory cellular infiltration within the myocardium with multinucleated giant cells and granulomas interspersed with lymphocytes. Microscopic field showed up to 10 multinucleated giant cells. In this case, there were focal areas at multiple locations and caused uneven thickness in the left ventricle wall. Idiopathic GCM is very rare and causation of hemopericardium is the unique feature of this case. In this case the direct link of GCM with aortitis and rupture of left ventricle wall resulting in hemopericardium is shown. This case is documented through macroscopic as well as microscopic photographs in H&E, Ziel-Nelson, and GMS staining.

Histophilus somni-associated syndromes in sheep from Southern Brazil.

PubMed

Headley, Selwyn A; Pereira, Alfredo H T; Balbo, Luciana C; Di Santia, Giovana W; Bracarense, Ana P F R L; Filho, Luiz F C Cunha; Schade, Jackson; Okano, Werner; Pereira, Priscilla F V; Morotti, Fábio; Preto-Giordano, Lucienne G; Marcasso, Rogério A; Alfieri, Alice F; Lisbôa, Júlio A N; Alfieri, Amauri A

2018-03-15

Histophilus somni is a Gram-negative bacterium that is associated with a disease complex (termed histophilosis) that can produce several clinical syndromes predominantly in cattle, but also in sheep. Histophilosis is well described in North America, Canada, and in some European countries. In Brazil, histophilosis has been described in cattle with respiratory, reproductive, and systemic disease, with only one case described in sheep. This report describes the occurrence of Histophilus somni-associated disease in sheep from Southern Brazil. Eight sheep with different clinical manifestations from five farms were investigated by a combination of pathological and molecular diagnostic methods to identify additional cases of histophilosis in sheep from Brazil. The principal pathological lesions were thrombotic meningoencephalitis, fibrinous bronchopneumonia, pulmonary abscesses, and necrotizing myocarditis. The main clinical syndromes associated with H. somni were thrombotic meningoencephalitis (n=4), septicemia (n=4), bronchopneumonia (n=4), and myocarditis (n=3). H. somni DNA was amplified from multiple tissues of all sheep with clinical syndromes of histophilosis; sequencing confirmed the PCR results. Further, PCR assays to detect Pasteurella multocida and Mannheimia haemolytica were negative. These findings confirmed the participation of H. somni in the clinical syndromes investigated during this study, and adds to the previous report of histophilosis in sheep from Brazil. Copyright © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Extracorporeal Cardiopulmonary Resuscitation Among Patients with Structurally Normal Hearts.

PubMed

Conrad, Stephanie J; Bridges, Brian C; Kalra, Yuvraj; Pietsch, John B; Smith, Andrew H

Extracorporeal cardiopulmonary resuscitation (eCPR) has been well described as a rescue therapy in refractory cardiac arrest among patients with congenital heart disease. The purpose of this retrospective analysis of data from the Extracorporeal Life Support Organization was to evaluate outcomes of eCPR in patients with structurally normal hearts and to identify risk factors that may contribute to mortality. During the study period, 1,431 patients met inclusion criteria. Median age was 16 years. Overall survival to hospital discharge was 32%. Conditional logistic regression demonstrated an independent survival benefit among smaller patients, patients with a lower partial pressure of carbon dioxide (PaCO2) on cannulation, and those with a shorter duration from intubation to eCPR cannulation. A diagnosis of sepsis was independently associated with a nearly threefold increase in odds of mortality, whereas the diagnosis of myocarditis portended a more favorable outcome. Neurologic complications, pulmonary hemorrhage, disseminated intravascular coagulation, CPR, pH less than 7.20, and hyperbilirubinemia after eCPR cannulation were independently associated with an increase in odds of mortality. When utilizing eCPR in patients with structurally normal hearts, a diagnosis of sepsis is independently associated with mortality, whereas a diagnosis of myocarditis is protective. Neurologic complications and pulmonary hemorrhage while on extracorporeal membrane oxygenation (ECMO) are independently associated with mortality.

Inhibition of 12/15-LO ameliorates CVB3-induced myocarditis by activating Nrf2.

PubMed

Ai, Feng; Zheng, Jiayong; Zhang, Yanwei; Fan, Taibing

2017-06-25

Cardiac 12/15-lipoxygenase (12/15-LO) was reported to be markedly up-regulated and involved in the development of heart failure. Nuclear factor E2-related factor 2 (Nrf2) plays anti-inflammatory and anti-oxidation roles in response to oxidative stress. However, the role of 12/15-LO in viral myocarditis (VMC) and its underlying molecular mechanism have not yet been elucidated. Here, we demonstrated that 12/15-LO was up-regulated and Nrf2 was down-regulated in coxsackievirus B3 (CVB3)-infected mice and cardiac myocytes. Baicalein, the specific inhibitor of 12/15-LO, was employed to investigate the role of 12/15-LO and its underlying mechanism in VMC. We found that baicalein treatment alleviated CVB3-induced VMC mouse models, as demonstrated by less inflammatory lesions in the heart tissues and less CK-MB level. Moreover, baicalein treatment attenuated CVB3-induced inflammatory cytokine production and oxidative stress. Mechanistic analysis suggested that baicalein treatment relieved CVB3-induced reduction of Nrf2 and heme oxygenase-1 (HO-1) expressions. Taken together, our study indicated that inhibition of 12/15-LO ameliorates VMC by activating Nrf2, providing a new therapeutic strategy for the therapy of VMC. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies.

PubMed

Koutkias, Vassilis G; Lillo-Le Louët, Agnès; Jaulent, Marie-Christine

2017-02-01

Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance. Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage. The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework. This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.

Complications of varicella zoster.

PubMed

Gücüyener, Kivilcim; Citak, Elvan Cağlar; Elli, Murat; Serdaroğlu, Ayse; Citak, Funda Erkasar

2002-02-01

Primary infection with varicella zoster is characterzed by a generalized vesicular rash usually without significant systemic illness. Encephalitis, pneumonitis, pancreatitis, nephritis, Reye and Guillan-Barre syndrome transvers myelitis, myocarditis have been reported before, but there is not any case having all these system to be involved during the same infection in a sequential manner ending up with multiorgan failure. We wanted to represent 21-month-old boy had a multiorgan failure due to varicella zoster infection.

Heterogeneity in the A33 Protein Impacts the Cross-Protective Efficacy of a Candidate Smallpox DNA Vaccine

DTIC Science & Technology

2008-01-01

include myocarditis, progressive vaccinia, eczema vaccinatum, and even death (Bray, 2003; Cassimatis et al., 2004; Eckart et al., 2004;Kretzschmaret...hundreds of genes, many of which encode for immunomodulatory molecules or molecules with unknown function . The safety risks posed by these molecules...1G10 or function indirectly by impacting the conformation of the physical epitope. However, findings in the literature support the conclusion that

A Clinical and Follow-up Study of Right and Left Bundle Branch Block

DTIC Science & Technology

1974-09-03

atrial septal defects, one with a patent dnctus arteriosns. and one with coarctation of the aorta and aortic stenosis ), one case of rheumatic heart...disease with mild mitral and aortic insufficiency, one case of documented myocarditis, and two cases of nonrheumatic hemodynamiially in- Tuhle 3 .Si...f,’r(»i/() Aniiltjsi\\ of Clinical Evahtotion in EliliB Stihjcrts significant mitral insufficiency. Since some of the ECG subgroups

Corynebacterial pneumonia in an African hedgehog.

PubMed

Raymond, J T; Williams, C; Wu, C C

1998-04-01

A 3-mo-old, male African hedgehog (Atelerix albiventris) was anorectic and lethargic for a period of 3 days prior to death. Necropys revealed lungs that were diffusely firm, dark red, and dorsally adhered by fibrinous tags to the pericardial sac. Histopathology revealed necrosuppurative bronchopneumonia with pulmonary abscesses and suppurative pericarditis and myocarditis. A Corynebacterium sp. was isolated from the lungs. We believe this is the first reported case of corynebacterial pneumonia in an African hedgehog.

Effect of QiShenYiQi pill on myocardial collagen metabolism in experimental autoimmune myocarditis rats.

PubMed

Lv, Shi-Chao; Wu, Meifang; Li, Meng; Wang, Qiang; Wang, Xiao-Jing; Zhang, Ao; Xu, Ling; Zhang, Jun-Ping

2017-04-01

To observe the effect of QiShenYiQi pill (QSYQ) on myocardial collagen metabolism in experimental autoimmune myocarditis rats, and to explore its mechanism of action. Lewis rats underwent the injection of myocardial myosin mixed with freund's complete adjuvant were randomized into three groups: model, valsartan and QSYQ groups. And we treated rats which were injected phosphate buffered saline (PBS) mixed with freund's complete adjuvant as control group. Rats were intervened and euthanized at 4 and 8 weeks. We use alkaline hydrolysis to detect the content of myocardial hydroxyproline (HYP), and ELISA to detect the level of serum procollagen type I carboxyterminal peptide (PICP), procollagen type III amino-terminal peptide (PIIINP), and collagen C telopeptide type I (CTX-I). Myocardial MMP-1 and TIMP-1 protein expression was detected by immunohistochemistry, and myocardial MMP-1 and TIMP-1 mRNA expression was detected by real-time qPCR. QSYQ reduced the content of myocardial HYP, and this reduction was greater over time. QSYQ also reduced the serum concentration of PICP, PIIINP, CTX-I and the PICP/PIIINP ratio, which further reduced over time, whereas its effect on lowering PICP was significantly greater than that of valsartan at 4 and 8 weeks, and lowering CTX-I was significantly greater than that of valsartan at 8 weeks. In addition, after 4 weeks, QSYQ enhanced the protein and mRNA expression of MMP-1 and TIMP-1, and its effect on highering TIMP-1 was significantly greater than that of valsartan, whereas there was no significant difference in the expression of myocardial MMP-1 or TIMP-1 at 8 weeks. QSYQ reduced the ratio of MMP-1/TIMP-1, which further reduced over time, and the effect of QYSQ was significantly greater than that of valsartan after 4 weeks. This study provides evidence that QSYQ can reduce the rate of myocardial collagen synthesis and degradation. It also effectively improved the degree of myocardial fibrosis in experimental autoimmune myocarditis rats and it had a tendency to have a greater effect with longer treatment duration, which is related to the mechanism of regulation of MMP-1 and TIMP-1 expression in the myocardial rat. Copyright © 2017. Published by Elsevier Masson SAS.

Complete Freund's adjuvant induces experimental autoimmune myocarditis by enhancing IL-6 production during initiation of the immune response.

PubMed

Fontes, Jillian A; Barin, Jobert G; Talor, Monica V; Stickel, Natalie; Schaub, Julie; Rose, Noel R; Čiháková, Daniela

2017-06-01

Complete Freund's Adjuvant (CFA) emulsified with an antigen is a widely used method to induce autoimmune disease in animal models, yet the contribution of CFA to the immune response is not well understood. We compared the effectiveness of CFA with Incomplete Freund's Adjuvant (IFA) or TiterMax Gold Adjuvant (TMax) in experimental autoimmune myocarditis (EAM) in male mice. EAM was induced in A/J, BALB/c, and IL6KO BALB/c male mice by injection of the myocarditogenic peptide in CFA, IFA, or TMax on days 0 and 7. EAM severity was analyzed by histology on day 21. In addition, specific flow cytometry outcomes were evaluated on day 21. Only mice immunized with CFA and myocarditogenic peptide on both days 0 and 7 developed substantial myocarditis as measured by histology. We observed a significantly increased level of IL6 in the spleen 3 days after CFA immunization. In the spleen and heart on day 21, there was an expansion of myeloid cells in CFA-immunized mice, as compared to IFA or TMax-immunized animals. Recombinant IL-6 at the time of IFA immunization partially restored susceptibility of the mice to EAM. We also treated EAM-resistant IL-6 knockout mice with recombinant IL-6 around the time of the first immunization, on days -1 to 2, completely restoring disease susceptibility, showing that the requirement for IL-6 coincides with primary immunization. Examining APC populations in the lymph node draining the immunization site evidenced the contribution of IL-6 to the CFA-dependence of EAM was through controlling local dendritic cell (DC) trafficking. CFA used with myocarditogenic peptide twice is required to induce EAM in both A/J and Balb/c mice. Although IFA and TiterMax induce antibody responses, only CFA preferentially induced autoantigen-specific responses. CFA expands monocytes in the heart and in the spleen. IL-6 signaling is required during short window around primary immunization to induce EAM. In addition, IL-6 deficient mice resistance to EAM could be reversed by injecting IL-6 around first immunization. IL-6 expands dendritic cell and monocytic populations and ultimately leads to a robust T-cell driven immune response in CFA immunized mice. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

[Myocardial regional thickness in patients with and without cardiomyopathy assessed by cardiac magnetic resonance].

PubMed

de Zan, Macarena; Carrascosa, Patricia; Deviggiano, Alejandro; Capuñay, Carlos; Rodríguez-Granillo, Gastón A

To explore regional differences in myocardial wall thickness (WT) among the most prevalent cardiomyopathies and in individuals without structural heart disease using cardiac magnetic resonance. Patients older than 18 years referred to cardiac magnetic resonance during the period between January 2014 and September 2014, with a diagnosis of hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy, ischemic cardiomyopathy, and myocarditis were retrospectively selected from our database. One hundred twenty patients patients were included. The control group had an average WT of 5.9±1.1mm, with a WT index of 2.9±0.8. Significantly lower mean WT in the apical segments were identified in both the control group (basal 6.7±1.3 vs. mid 6.0±1.3 vs. apical 4.6±1.0mm, P<.0001) and in all evaluated cardiomyopathies (hypertrophic cardiomyopathy: basal 10.5±2.4 vs. mid 10.8±2.7 vs. apical 7.3±3.3mm, P<.0001; idiopathic dilated cardiomyopathy: basal 7.7±1.7 vs. mid 7.6±1.3 vs. apical 5.4±1.3mm, P<.0001; ischemic cardiomyopathy: basal 7.4±1.7 vs. mid 7.5±1.9 vs. apical 5.5±1.8mm, P<.0001; myocarditis: basal 7.1±1.5 vs. mid 6.4±1.1 vs. apical 5.1±0.8, P<.0001). Significant gender differences were also evident regarding the mean WT both in the control group (male 6.5±2.1 vs. female 5.2±1.7mm, P<.0001), as in hypertrophic cardiomyopathy (10.5±5.3 vs. 8.5±5.7mm, P<.0001) and myocarditis (6.6±2.0 vs. 5.2±1.6mm, P<.0001). We found a relatively high prevalence of segments commonly deemed thinned among patients without structural heart disease. We also observed a marked asymmetry and longitudinal gradient in wall thickness both in controls and in the various cardiomyopathies evaluated. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Mammalian Toxicity of Munition Compounds. Phase II. Effects of Multiple Doses. Part III. 2,6-Dinitrotoluene

DTIC Science & Technology

1976-07-01

Histopathology , Statistical Analysis, and Normal Values ..... ...... ........... 131 I Ii A.mmALIAN TOXICITY OF MUNITION COMPOUNDS PHASE II: Effects of...chemistry tests and histopathology , and the normal values are given in Appendix I. The concentrations of Ca 2+, Mg2 +, Na+ and K+ in serum were determined...mice fed 2,6-DNT included focal epicarditis or myocarditis, focal cystitis, chronic murine pneumonia or bronchopneumonia, metritis and focal myositis

Clinical and Pathologic Characteristics of Myocarditis as a Cause of Sudden Death

DTIC Science & Technology

2008-01-01

Polio Adenovirus Hepatitis B and C HIV Trypanosomiasis cruzi Toxoplasmosis  gondi Spirochetal Borrelia burgdorferi N i f ti   M dition n ec ous yocar s...0.265 Prodromal symptoms Fever, headache, URI  symptoms 16/23 (69.6%) 13/23 (56.5%)   48/99 (48.5%) 0/99 (0.0%) 0.104 ɘ.001 Out of hospital death 5 (16.7

PAR-1 contributes to the innate immune response during viral infection

PubMed Central

Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

2013-01-01

Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

T1 and T2 Mapping in Cardiology: "Mapping the Obscure Object of Desire".

PubMed

Mavrogeni, Sophie; Apostolou, Dimitris; Argyriou, Panayiotis; Velitsista, Stella; Papa, Lilika; Efentakis, Stelios; Vernardos, Evangelos; Kanoupaki, Mikela; Kanoupakis, George; Manginas, Athanassios

The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing. © 2017 S. Karger AG, Basel.

Scleroderma Renal Crisis: A Reversible Cause of Left Ventricular Dysfunction.

PubMed

Martínez-Milla, Juan; Gaebelt, Hans Paul; Sánchez-Pernaute, Olga; Kallmeyer, Andrea; Romero, José; Farré, Jerónimo

2018-05-02

We report a case of acute left ventricular dysfunction due to myocarditis, in the setting of a scleroderma renal crisis. The case is particularly intriguing for the favorable outcome of both symptoms and heart function following immunosuppressive therapy. We also highlight the changes observed over time with image techniques as well as in electrocardiograms. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

Encephalomyocarditis virus in a captive Malayan tapir (Tapirus indicus)

PubMed Central

Vercammen, Francis; Bosseler, Leslie; Tignon, Marylène; Cay, Ann Brigitte

2017-01-01

A 5-month-old female captive Malayan tapir (Tapirus indicus) died suddenly without preceding symptoms. Gross necropsy revealed numerous white circular and linear foci in the myocard. Differential diagnosis all turned out negative, except for encephalomyocarditis virus. Histopathology revealed mineralisation of myocardial cells and interstitial infiltration of lymphocytes, plasma cells and less neutrophils. Encephalomyocarditis virus was detected by PCR. Although encephalomyocarditis virus occurs in many mammals, this is the first published description of this virus in a Malayan tapir. PMID:28616390

Encephalomyocarditis virus in a captive Malayan tapir (Tapirus indicus).

PubMed

Vercammen, Francis; Bosseler, Leslie; Tignon, Marylène; Cay, Ann Brigitte

2017-01-01

A 5-month-old female captive Malayan tapir ( Tapirus indicus ) died suddenly without preceding symptoms. Gross necropsy revealed numerous white circular and linear foci in the myocard. Differential diagnosis all turned out negative, except for encephalomyocarditis virus. Histopathology revealed mineralisation of myocardial cells and interstitial infiltration of lymphocytes, plasma cells and less neutrophils. Encephalomyocarditis virus was detected by PCR. Although encephalomyocarditis virus occurs in many mammals, this is the first published description of this virus in a Malayan tapir.

Necropsy and histopathologic findings in 14 African hedgehogs (Atelerix albiventris): a retrospective study.

PubMed

Raymond, J T; White, M R

1999-06-01

From fiscal years 1992 through 1996, 14 African hedgehog (Atelerix albiventris) cases were submitted to the Animal Disease Diagnostic Laboratory at Purdue University. The most common diagnoses were splenic extramedullary hematopoiesis (91%), hepatic lipidosis (50%), renal disease (50%), and neoplastic disease (29%). Other less frequent necropsy findings were myocarditis (21%), colitis (14%), bacterial septicemia (14%), and pneumonia (14%). The data indicate that splenic extramedullary hematopoiesis, hepatic lipidosis, renal disease, and neoplasms are frequent postmortem findings in hedgehogs.

Aviator's Heart: A Case of Athlete's Heart in an Active Duty Male Naval Aviator.

PubMed

Ryaboy, Ilya V; Watts, James A; Barnwell, Megan L

2018-05-31

Athlete's heart is the condition of cardiac remodeling as a result of physiologic stress induced by regular strenuous physical activity by professional or elite amateur individuals. The literature describes several characteristics of the athletic heart, including left ventricular hypertrophy, increased left ventricular mass, right ventricular dilatation, atrial enlargement, electrocardiographic changes, and abnormalities on cardiac magnetic resonance imaging. We present a case of athletic heart in an exceptionally physically fit active duty naval aviator who experienced syncope and underwent extensive cardiac testing. He was found to have borderline hypertrophic changes as well as delayed gadolinium enhancement initially concerning for myocarditis. Cardiopulmonary exercise testing revealed an exercise capacity of 120% above the maximum measurable value for his age and gender. He was then diagnosed with athlete's heart and released to active duty with no limitations to his flight status. A challenge is posed to the practicing clinician in differentiating the athletic heart from the heart of an athlete suffering from underlying pathophysiology. Athlete's heart is an elusive diagnosis and may be associated with findings concerning for more insidious pathology, including hypertrophic cardiomyopathy and dilated cardiomyopathy. Additionally, patients with athlete's heart have been noted to have delayed gadolinium enhancement similar to that seen in patients with a history of myocarditis; the clinical significance of this finding is yet to be fully elucidated. In a military setting, distinguishing the heart of the healthy and athletic service member from the unfortunate one who has cardiomyopathy remains an important clinical distinction warranting further study.

Unresolved issues in theories of autoimmune disease using myocarditis as a framework

PubMed Central

Root-Bernstein, Robert; Fairweather, DeLisa

2014-01-01

Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. PMID:25484004

Unresolved issues in theories of autoimmune disease using myocarditis as a framework.

PubMed

Root-Bernstein, Robert; Fairweather, DeLisa

2015-06-21

Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of toll-like receptors in cardiovascular diseases.

PubMed

Vallejo, Jesus G

2011-07-01

The discovery and characterization of the TLR (Toll-like receptor) family has led to a better understanding of the innate immune system. The strategy of innate immune recognition is based on the detection of constitutive and conserved products of micro-organisms. However, host molecules that are released during injury can also activate TLRs. Engagement of TLRs by microbial or host-derived molecules induces the expression of pro-inflammatory cytokines, which may have both beneficial and detrimental effects on the host. In addition to being expressed in immune cells, TLRs are expressed in other tissues such as those of the cardiovascular system. In the present review, the role of TLRs in septic cardiomyopathy, viral myocarditis, atherosclerosis, ischaemia/reperfusion injury and cardiac remodelling after myocardial infarction are outlined, with attention paid to genetically modified murine models. Although much has been learned about stress-induced TLR activation in the tissues of the cardiovascular system, the role of individual TLRs in initiating and integrating homoeostatic responses within the heart remains to be defined. Accumulating evidence indicates that TLRs may play an important role in the pathogenesis of atherosclerosis, viral myocarditis, dilated cardiomyopathy, cardiac allograft rejection and sepsis-induced left ventricular dysfunction. Moreover, heart failure of diverse aetiology is also now recognized to have an important immune component, with TLR signalling influencing the process of cardiac remodelling and prognosis. In the present review, we outline the biology of TLRs as well as the current experimental and clinical evidence for the role of TLRs in cardiovascular diseases.

Immunohistochemical identification of Propionibacterium acnes in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients.

PubMed

Asakawa, Naoya; Uchida, Keisuke; Sakakibara, Mamoru; Omote, Kazunori; Noguchi, Keiji; Tokuda, Yusuke; Kamiya, Kiwamu; Hatanaka, Kanako C; Matsuno, Yoshihiro; Yamada, Shiro; Asakawa, Kyoko; Fukasawa, Yuichiro; Nagai, Toshiyuki; Anzai, Toshihisa; Ikeda, Yoshihiko; Ishibashi-Ueda, Hatsue; Hirota, Masanori; Orii, Makoto; Akasaka, Takashi; Uto, Kenta; Shingu, Yasushige; Matsui, Yoshiro; Morimoto, Shin-Ichiro; Tsutsui, Hiroyuki; Eishi, Yoshinobu

2017-01-01

Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect Propionibacterium acnes, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients. We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P. acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (≥14 inflammatory cells) and minimal (<14 inflammatory cells) inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS-group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18 (46%) of the CM-group samples. P. acnes-positive reactivity in granulomas, massive inflammatory foci, and minimal inflammatory foci were detected in 10 (63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none of the M-group and CM-group samples. Frequent identification of P. acnes in sarcoid granulomas of originally aseptic myocardial tissues suggests that this indigenous bacterium causes granuloma in many CS patients. IHC detection of P. acnes in massive or minimal inflammatory foci of myocardial biopsy samples without granulomas may be useful for differentiating sarcoidosis from myocarditis or other cardiomyopathies.

Evaluation of a rapid detection for Coxsackievirus B3 using one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP).

PubMed

Monazah, A; Zeinoddini, M; Saeeidinia, A R

2017-08-01

Coxsackievirus B3 (CVB3) is a member of the genus Enterovirus within the family Picornaviridae and is an important pathogen of viral myocarditis, which accounts for more than 50% viral myocarditis cases. VP1 is major capsid protein that this region has a low homology in both amino acid and nucleotide sequences among Enteroviruses. Therefore we have chosen this region for designed a set of RT-LAMP primers for CVB3 detection. For this the total RNA was extracted from 24-h post infected-HeLa cells with complete cytopathic effect (CPE), and applied to a one-step reverse transcription loop-mediated isothermal amplification reaction (RT-LAMP) using CVB3-specific primers. The optimization of RT-LAMP reaction was carried out with three variables factors including MgSO 4 concentration, temperature and time of incubation. Amplification was analyzed by using 2% agarose gel electrophoresis and ethidium bromide and SYBR Green staining. Our results were shown the ladder-like pattern of the VP1 gene amplification. The LAMP reaction mix was optimized and the best result observed at 4mM MgSO 4 and 60°C for 90min incubation. RT-LAMP had high sensitivity and specificity for detection of CVB3 infection. This method can be used as a rapid and easy diagnostic test for detection of CVB3 in clinical laboratories. Copyright © 2017 Elsevier B.V. All rights reserved.

Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease.

PubMed

Suganuma, Eisuke; Niimura, Fumio; Matsuda, Shinichi; Ukawa, Toshiko; Nakamura, Hideaki; Sekine, Kaori; Kato, Masahiko; Aiba, Yuji; Koga, Yasuhiro; Hayashi, Kuniyoshi; Takahashi, Osamu; Mochizuki, Hiroyuki

2017-04-01

Kawasaki disease is a common systemic vasculitis that leads to coronary artery lesions. Besides its antihypertensive effects, losartan can modulate inflammation in cardiovascular disease. We examined whether losartan can attenuate coronary inflammation in a murine model of Kawasaki disease. Five-wk-old C57/BL6J male mice were intraperitoneally injected with Lactobacillus casei cell wall extract to induce coronary inflammation and divided into four groups: placebo, intravenous immunoglobulin (IVIG), losartan, and IVIG+losartan. After 2 wk, mice were harvested. The coronary perivasculitis was significantly attenuated by losartan but not by IVIG alone, and further dramatic attenuation by IVIG+losartan was observed. The frequency of Lactobacillus casei cell wall extract-induced myocarditis (80%) was markedly lowered by losartan (22%) and IVIG+losartan (0%). Furthermore, interleukin (IL)-6 mRNA was markedly attenuated by IVIG+losartan. Serum levels of IL-6, TNF-α, MCP-1, and IL-10 after Lactobacillus casei cell wall extract injection were slightly decreased by IVIG or losartan. Moreover, IL-1β, IL-10, and MCP-1 levels were significantly decreased by IVIG+losartan. The addition of losartan to IVIG strongly attenuated the severity of coronary perivasculitis and the incidence of myocarditis, along with suppressing systemic/local cytokines as well as the activated macrophage infiltration. Therefore, losartan may be a potentially useful additive drug for the acute phase of Kawasaki disease to minimize coronary artery lesions.

Toxicological effect of TiO2 nanoparticle-induced myocarditis in mice

NASA Astrophysics Data System (ADS)

Hong, Fashui; Wang, Ling; Yu, Xiaohong; Zhou, Yingjun; Hong, Jie; Sheng, Lei

2015-08-01

Currently, impacts of exposure to TiO2 nanoparticles (NPs) on the cardiovascular system are not well understood. The aim of this study was to investigate whether TiO2 NPs induce myocarditis and its underlying molecular mechanism in the cardiac inflammation in mice. Mice were exposed to TiO2 NPs for 6 months; biochemical parameters of serum and expression of Th1-related and Th2-related cytokines in the heart were investigated. The results showed that TiO2 NP exposure resulted in cardiac lesions coupling with pulmonary inflammation; increases of aspartate aminotransferase (AST), creatine kinase (CK), C-reaction protein (CRP), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels; and a reduction of nitric oxide (NOx) level in the serum. These were associated with increases of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, transforming growth factor-β (TGF-β), creatine kinase, CRP, adhesion molecule-1, and monocyte chemoattractant protein-1, interferon-γ (IFN-γ), signal transducers and activators of transcription (STAT)1, STAT3, or STAT6, GATA-binding domain-3, GATA-binding domain-4, endothelin-1 expression levels, and T-box expressed in T cells expression level that is the master regulator of pro-inflammatory cytokines and transcription factors in the heart. These findings imply that TiO2 NP exposure may increase the occurrence and development of cardiovascular diseases.

Adult Kawasaki's disease with myocarditis, splenomegaly, and highly elevated serum ferritin levels.

PubMed

Cunha, Burke A; Pherez, Francisco M; Alexiadis, Varvara; Gagos, Marios; Strollo, Stephanie

2010-01-01

Kawasaki's disease is a disease of unknown cause. The characteristic clinical features of Kawasaki's disease are fever> or =102 degrees F for> or =5 days accompanied by a bilateral bulbar conjunctivitis/conjunctival suffusion, erythematous rash, cervical adenopathy, pharyngeal erythema, and swelling of the dorsum of the hands/feet. Kawasaki's disease primarily affects children and is rare in adults. In children, Kawasaki's disease is more likely to be associated with aseptic meningitis, coronary artery aneurysms, and thrombocytosis. In adult Kawasaki's disease, unilateral cervical adenopathy, arthritis, conjunctival suffusion/conjunctivitis, and elevated serum transaminases (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) are more likely. Kawasaki's disease in adults may be mimicked by other acute infections with fever and rash, that is, group A streptococcal scarlet fever, toxic shock syndrome (TSS), and Rocky Mountain Spotted Fever (RMSF). Because there are no specific tests for Kawasaki's disease, diagnosis is based on clinical criteria and the syndromic approach. In addition to rash and fever, scarlet fever is characterized by circumoral pallor, oropharyngeal edema, Pastia's lines, and peripheral eosinophilia, but not conjunctival suffusion, splenomegaly, swelling of the dorsum of the hands/feet, thrombocytosis, or an elevated SGOT/SGPT. In TSS, in addition to rash and fever, there is conjunctival suffusion, oropharyngeal erythema, and edema of the dorsum of the hands/feet, an elevated SGOT/SGPT, and thrombocytopenia. Patients with TSS do not have cervical adenopathy or splenomegaly. RMSF presents with fever and a maculopapular rash that becomes petechial, first appearing on the wrists/ankles after 3 to 5 days. RMSF is accompanied by a prominent headache, periorbital edema, conjunctival suffusion, splenomegaly, thrombocytopenia, an elevated SGOT/SGPT, swelling of the dorsum of the hands/feet, but not oropharyngeal erythema. We present a case of adult Kawasaki's disease with myocarditis and splenomegaly. The patient's myocarditis rapidly resolved, and he did not develop coronary artery aneurysms. In addition to splenomegaly, this case of adult Kawasaki's disease is remarkable because the patient had highly elevated serum ferritin levels of 944-1303 ng/mL; (normal<189 ng/mL). To the best of our knowledge, this is the first report of adult Kawasaki's disease with highly elevated serum ferritin levels. This is also the first report of splenomegaly in adult Kawasaki's disease. We conclude that Kawasaki's disease should be considered in the differential diagnosis in adult patients with rash/fever for> or =5 days with conjunctival suffusion, cervical adenopathy, swelling of the dorsum of the hands/feet, thrombocytosis and otherwise unexplained highly elevated ferritin levels. Copyright 2010 Elsevier Inc. All rights reserved.

Myopericarditis during a primary Epstein-Barr virus infection in an otherwise healthy young adult. An unusual and insidious complication. Case report and a 60-year literature review.

PubMed

Sabbatani, Sergio; Manfredi, Roberto; Ortolani, Paolo; Trapani, Fabio Filippo; Viale, Pierluigi

2012-06-01

An otherwise healthy young man had infectious mononucleosis detected after an atypical clinical onset, including myocarditis and pericarditis. Our patient slowly but completely recovered from his cardiac complications after the course of his primary Epstein-Barr infection, as shown by periodical electrocardiographic and ultrasonographic studies, and a simple treatment with aspirin alone. Our case report is briefly reported, and discussed with regard to the existing literature, which has recorded such complications since the mid 1940s.

Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan.

PubMed

Suzuki, Shigeaki; Ishikawa, Nobuhisa; Konoeda, Fumie; Seki, Nobuhiko; Fukushima, Satoshi; Takahashi, Kikuko; Uhara, Hisashi; Hasegawa, Yoshikazu; Inomata, Shinichiro; Otani, Yasushi; Yokota, Kenji; Hirose, Takashi; Tanaka, Ryo; Suzuki, Norihiro; Matsui, Makoto

2017-09-12

To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 women with a mean age of 73.5 ± 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity. The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important. © 2017 American Academy of Neurology.

Pathologic findings in red-tailed hawks (Buteo jamaicensis) and Cooper's hawks (Accipiter cooper) naturally infected with West Nile virus.

PubMed

Wünschmann, Arno; Shivers, Jan; Bender, Jeff; Carroll, Larry; Fuller, Susan; Saggese, Miguel; van Wettere, Arnaud; Redig, Pat

2004-09-01

Carcasses of 13 red-tailed hawks (RTHAs) and 11 Cooper's hawks (COHAs) were tested for West Nile virus (WNV) using WNV-specific reverse transcriptase-polymerase chain reaction (RT-PCR) on fresh brain tissue and WNV-specific immunohistochemistry (IHC) on various organs. Ten COHAs (91%) and 11 RTHAs (85%) were positive for WNV RNA by RT-PCR. All 11 COHAs (100%) and 10 RTHAs (77%) were positive for WNV antigen by IHC. A triad of inflammatory lesions, including chronic lymphoplasmacytic and histiocytic encephalitis, endophthalmitis, and myocarditis, was common in both species. In COHAs, the heart (54%), cerebrum (50%), and eye (45%) were the organs that most commonly contained WNV antigen. The amount of WNV antigen was usually small. In RTHAs, the kidney (38%), cerebrum (38%), cerebellum (38%), and eye (36%) were the organs most commonly containing WNV antigen. Unlike COHAs, larger amounts of WNV antigen were present in the cerebrum of RTHAs. WNV antigen was detected in similar cell populations in both species, including neurons of brain, spinal cord, and retina, pigmented epithelial cells of the retina, epithelial cells of renal medullary tubules, cardiomyocytes, endothelial cells and smooth muscle cells of arteries, dendritic cells of splenic lymph follicles, exocrine pancreatic cells, adrenal cells, and keratinocytes of the skin. The study presents strong evidence that WNV can cause a chronic fatal disease in RTHAs and COHAs. The lesion distribution of WNV infection in both species is variable, but inflammatory lesions are common, and a triad of lesions including encephalitis, myocarditis, and endophthalmitis is indicative of WNV infection in both species.

Neosporosis-associated bovine abortion in Pennsylvania.

PubMed

Hattel, A L; Castro, M D; Gummo, J D; Weinstock, D; Reed, J A; Dubey, J P

1998-01-31

Neospora caninum was found in fetal tissues of 34 of 688 cases of bovine abortion submitted to the Pennsylvania Animal Diagnostic Laboratory System during the period from May 1994 to November 1996. The aborted fetuses ranged in gestational age from 3 to 8 months. Microscopic lesions consisted primarily of encephalitis and myocarditis. A labeled (strept) avidin-biotin staining procedure using anti-N. caninum polyclonal rabbit serum revealed N. caninum organisms within the fetal brain (27 of 27), heart (10 of 13), placenta (5 of 6), kidney (2 of 2), liver (1 of 4) and skeletal muscle (1 of 1).

[Trombosis of the middle cerebral artery as the cause of cerebrovascular insult (CVI) and recognition of the etiologic factors for CVI].

PubMed

Hajro, Tarik; Ramić, Ibrahim; Alajbegović, Azra

2004-01-01

In the paper is shown the case of the patient of the CVI life, age of 40 years. It was about the vascular lesion left of the temperoparienal MRA shew the amputation of amputation of the temporal branches art. cerebri medii from the left side. The patient 6 years before she suffered of CVI infract myocard after which she recovered well. After the performed neurologic and physiatric treatment it came to the strength of the rude motor strength with the normalization of the speech.

Mesalamine-induced myopericarditis in a paediatric patient with Crohn's disease.

PubMed

Nair, Asha G; Cross, Russell R

2015-04-01

Mesalamine-containing products are considered first-line treatment for inflammatory bowel disease. Myocarditis is recognised as a very rare possible side effect of these medications, but has not often been described in the paediatric population. We present a case of an adolescent with Crohn's disease who presented with myopericarditis after recent initiation of Pentasa. Once identified as the causative agent, the drug was discontinued, with subsequent normalisation of troponin and improvement of function. This case identifies the importance of prompt evaluation, diagnosis, and treatment of paediatric patients receiving mesalamine-containing medications that present with significant cardiovascular symptoms.

Disseminated visceral coccidiosis in whooping cranes

USGS Publications Warehouse

Carpenter, J.W.; Spraker, T.R.; Novilla, M.N.

1980-01-01

Three 13- to 18-day-old whooping cranes (Grus americana) and a 9-year-old whooping crane died in outdoor pens at the Patuxent Wildlife Research Center. The deaths were associated with an overwhelming systemic infection by an intracellular protozoan parasite, which resulted in enteritis, granulomatous bronchopneumonia, hepatitis, splenitis, and myocarditis. The clinical, histopathologic, and electron microscopic findings were similar to those in sandhill cranes (Grus canadensis) at the Patuxent Center found to be infected with Eimeria reichenowi and E gruis. Since these eimerian species also parasitize wild whooping cranes, this parasite might be an important pathogenic agent for this species.

Toxoplasmosis with hemophagocytic syndrome after bone marrow transplantation: diagnosis at autopsy.

PubMed

Duband, S; Cornillon, J; Tavernier, E; Dumollard, J-M; Guyotat, D; Péoc'h, M

2008-10-01

Toxoplasmosis is a rare but well recognized opportunistic infection that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Besides encephalitis, other common presentations of Toxoplasma gondii infection are interstitial pneumonitis and myocarditis. Because of its non-specific clinical and biological signs and its lethal outcome, toxoplasmosis is often misdiagnosed and only revealed at autopsy. We report a case of a postmortem diagnosis of disseminated toxoplasmosis associated with hemophagocytic syndrome, which underlines the value of necropsy in cases of death after transplantation. We also discuss clinical presentations and risk factors that lead to toxoplasmosis in allo-HSCT recipients.

The logistics and cost-effectiveness of circulatory support: advantages of the ABIOMED BVS 5000.

PubMed

Couper, G S; Dekkers, R J; Adams, D H

1999-08-01

In 1994, the ABIOMED BVS 5000 was incorporated into our acute cardiac assist armamentarium. This report is a general overview of our experience. A hypothetical cost analysis focusing on specific devices and device-related personnel contrasted the BVS 5000 with our prior model of centrifugal pump use. In 3 years, 22 patients were supported with the BVS 5000, as a biventricular assist device in 40%, right ventricular assist device in 27%, and left ventricular assist device in 32%. Indications were postcardiotomy support in 12, acute myocarditis in 2, bridge to transplant in 4, and failed heart transplant in 4. The cost analysis was performed retrospectively. The actual cost of disposable blood pumps, including replacement pumps, and cannulae constituted the BVS cost. The hypothetical centrifugal costs included the disposables, replacement cones, as well as the labor costs of the continuous perfusionist coverage. Of the 22 patients, 10 (45%) were weaned and 13 (59%) were successfully discharged. Five patients were transplanted while on BVS 5000 support, accounting for a higher rate of discharge. Comparison of "actual" BVS costs with "projected" centrifugal costs revealed differences based upon the intended application of the BVS. In bridge-to-transplant patients with long duration of support, the daily cost of support was dramatically lower with the BVS 5000. For short-term postcardiotomy support, acute myocarditis, or failed transplant, the differences were small. Because the BVS 5000 was readily managed by the intensive care unit nursing staff, this system displaced centrifugal systems in our program. Outcome measures of weaning and successful discharge were improved relative to our prior experience with centrifugal pumps. Even without taking indirect costs into account, the hypothetical cost analysis supported continued use of the BVS system for acute cardiac assistance.

Comparison of myocardial damage among dogs at different stages of clinical leishmaniasis and dogs with idiopathic chronic kidney disease.

PubMed

Martínez-Hernández, L; Casamian-Sorrosal, D; Barrera-Chacón, R; Cuesta-Gerveno, J M; Belinchón-Lorenzo, S; Gómez Nieto, L C; Duque-Carrasco, F J

2017-03-01

Canine leishmaniasis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum. Myocarditis in CanL has been described previously in CanL by histopathological analysis of post-mortem specimens and by evaluation of cardiac troponin I (cTnI) levels. However, the degree of myocardial damage at different stages of CanL and the role that concurrent azotaemia plays in this myocardial injury are unknown. The aim of this study was to prospectively evaluate and compare the presence of myocardial injury in dogs at different stages of clinical CanL and in dogs with severe idiopathic chronic kidney disease (CKD) by measuring cTnI. Forty-eight dogs were included in the study, divided into four groups: (1) group A (10 healthy dogs); (2) group B (17 dogs with CanL without renal azotaemia, classified as mild to severe in the LeishVet scheme); (3) group C (11 dogs with CanL and renal azotaemia, classified as very severe in the LeishVet scheme); and (4) group D (10 dogs with idiopathic CKD). Dogs in group C had significantly higher cTnI than dogs in groups B and D, although cTnI was also elevated in these groups. Dogs in group A had normal cTnI values. Dogs in groups D and C had similar renal IRIS classification scorers. Severe lymphoplasmocytic myocarditis and a positive real time PCR of L. infantum DNA were observed in all dogs in group C. Dogs with very severe CanL exhibit more myocardial injury than dogs with milder CanL or dogs with idiopathic CKD. Copyright © 2016. Published by Elsevier Ltd.

Cerebral tuberculosis in a patient with systemic lupus erythematosus following cyclophosphamide treatment: a case report.

PubMed

Cooray, S; Zhang, H; Breen, R; Carr-White, G; Howard, R; Cuadrado, M; D'Cruz, D; Sanna, G

2018-04-01

Central nervous system (CNS) tuberculosis (TB) is a rare but catastrophic event in patients with systemic lupus erythematosus (SLE). Here we report a case of cerebral TB in a patient with lupus myocarditis and nephritis, following cyclophosphamide immunosuppression. To our knowledge this is the first reported case of cerebral TB in SLE in a non-endemic country. A 31-year-old female with SLE and a history of regular travel to Kenya presented to our centre with clinical features of acute heart failure. She was diagnosed with severe lupus myocarditis, and a renal biopsy also confirmed lupus nephritis. Prior to admission, she had also had a cough, fever and weight loss and was under investigation for suspected TB infection. She was treated with ivabradine, beta-blockers and diuretics together with methylprednisolone and cyclophosphamide immunosuppression. Subsequent sputum cultures confirmed TB and she was commenced on triple therapy. Despite this, she developed confusion, dizziness, blurred vision and fluctuating consciousness. Magnetic resonance imaging (MRI) and lumbar puncture revealed CNS TB infection resulting in meningitis. This was later complicated by obstructive hydrocephalus due to TB abscesses. A ventriculoperitoneal (VP) shunt was inserted and TB medications were given intravenously (IV) with dexamethasone. Following a prolonged hospital admission, the patient eventually recovered and rituximab treatment was used to control her SLE. TB infection has been associated with SLE flares. It is likely in this case that TB exacerbated a lupus flare and subsequent immunosuppression resulted in mycobacterial dissemination to the CNS. Systemic and CNS features of TB and SLE are difficult to distinguish and their contemporaneous management represents a diagnostic and therapeutic challenge.

Myocarditis in mice and guinea pigs experimentally infected with a canine-origin Borrelia isolate from Florida.

PubMed

Breitschwerdt, E B; Geoly, F J; Meuten, D J; Levine, J F; Howard, P; Hegarty, B C; Stafford, L C

1996-04-01

To characterize the pathogenic potential of a unique Borrelia isolate obtained from a dog from Florida (FCB isolate). Prospective experimental infection. 32 preweanling Swiss Webster mice and 12 adult male Hartley guinea pigs were injected intraperitoneally with 10(5) spirochetes. Mice were used as controls and blood recipients, and at 3- to 4-day intervals, 1 control mouse and 2 infected mice were necropsied, tissues were cultured, and a recipient mouse was inoculated with blood. Guinea pigs were randomized to 4 groups and inoculated intradermally with 10(0), 10(2), 10(3), or 10(4) spirochetes. For 48 days, clinical, hematologic, serologic, and microbiologic tests were performed on them, after which they were necropsied. In mice, spirochetemia was detectable between postinoculation days (PID) 3 and 13, and seroreactivity to homologous antigen was detectable during PID 10 through 31. Compared with control mice, infected mouse spleens were 2 to 3 times larger. Histologic lesions included lymphoid hyperplasia, neutrophilic panniculitis, epicarditis, and myocarditis, with intralesional spirochetes detected from PID 3 through 6. During PID 10 through 31, nonsuppurative epicarditis developed. Signs of illness and hematologic abnormalities were not observed in guinea pigs, despite isolating spirochetes from blood during PID 7 to 27. When necropsied on PID 48, histologic lesions included lymphoid hyperplasia and lymphocytic plasmacytic epicarditis. The FCB isolate causes spirochetemia, lymphoid hyperplasia, dermatitis, and myocardial injury in Swiss Webster mice and can be transmitted by blood inoculation. In Hartley guinea pigs, the isolate causes spirochetemia, lymphoid hyperplasia, and epicarditis. Documentation of disease in mice, guinea pigs, and, presumably, dogs raises the level of concern that the FCB isolate might be pathogenic for man and other animal species.

Cardiomyopathy Syndrome of Atlantic Salmon (Salmo salar L.) Is Caused by a Double-Stranded RNA Virus of the Totiviridae Family▿

PubMed Central

Haugland, Øyvind; Mikalsen, Aase B.; Nilsen, Pål; Lindmo, Karine; Thu, Beate J.; Eliassen, Trygve M.; Roos, Norbert; Rode, Marit; Evensen, Øystein

2011-01-01

Cardiomyopathy syndrome (CMS) of farmed and wild Atlantic salmon (Salmo salar L.) is a disease of yet unknown etiology characterized by a necrotizing myocarditis involving the atrium and the spongious part of the heart ventricle. Here, we report the identification of a double-stranded RNA virus likely belonging to the family Totiviridae as the causative agent of the disease. The proposed name of the virus is piscine myocarditis virus (PMCV). On the basis of the RNA-dependent RNA polymerase (RdRp) sequence, PMCV grouped with Giardia lamblia virus and infectious myonecrosis virus of penaeid shrimp. The genome size of PMCV is 6,688 bp, with three open reading frames (ORFs). ORF1 likely encodes the major capsid protein, while ORF2 encodes the RdRp, possibly expressed as a fusion protein with the ORF1 product. ORF3 seems to be translated as a separate protein not described for any previous members of the family Totiviridae. Following experimental challenge with cell culture-grown virus, histopathological changes are observed in heart tissue by 6 weeks postchallenge (p.c.), with peak severity by 9 weeks p.c. Viral genome levels detected by real-time reverse transcription (RT)-PCR peak earlier at 6 to 7 weeks p.c. The virus genome is detected by in situ hybridization in degenerate cardiomyocytes from clinical cases of CMS. Virus genome levels in the hearts from clinical field cases correlate well with the severity of histopathological changes in heart tissue. The identification of the causative agent for CMS is important for improved disease surveillance and disease control and will serve as a basis for vaccine development against the disease. PMID:21411528

Needles in Hay II: Detecting Cardiac Pathology by the Pediatric Chest Pain Standardized Clinical Assessment and Management Plan.

PubMed

Kane, David A; Friedman, Kevin G; Fulton, David R; Geggel, Robert L; Saleeb, Susan F

2016-09-01

To determine if patients evaluated using the pediatric chest pain standardized clinical assessment and management plan (SCAMP) in cardiology clinic were later diagnosed with unrecognized cardiac pathology, and to determine if other patients with cardiac pathology not enrolled in the SCAMP would have been identified using the algorithm. Patients 7-21 years of age, newly diagnosed with hypertrophic or dilated cardiomyopathy, coronary anomalies, pulmonary embolus, pulmonary hypertension, pericarditis, or myocarditis were identified from the Boston Children's Hospital (BCH) cardiac database between July 1, 2010 and December 31, 2012. Patients were cross-referenced to the SCAMP database or retrospectively assessed with the SCAMP algorithm. Among 98 patients with cardiac pathology, 34 (35%) reported chest pain, of whom 10 were diagnosed as outpatients. None of these patients were enrolled in the SCAMP because of alternate chief complaints (n = 4) or referral to BCH for management of the new diagnosis (n = 6). Each of these patients would have had an echocardiogram recommended by retrospective application of the SCAMP algorithm. Two other patients with cardiac pathology were among the 1124 patients assessed by the SCAMP. One patient initially diagnosed with noncardiac chest pain presented 18 months later and was diagnosed with myocarditis as an inpatient. One patient seen initially in the emergency department was subsequently diagnosed with pericarditis as an outpatient. Patients assessed by the chest pain SCAMP at BCH were not later diagnosed with cardiac pathology that was missed at the initial encounter. Nonenrolled outpatients with cardiac pathology and chest pain would have been successfully identified with the SCAMP algorithm. © 2016 Wiley Periodicals, Inc.

Data from a nationwide registry on sports-related sudden cardiac deaths in Germany

PubMed Central

Scharhag, Jürgen; Meyer, Tim

2015-01-01

Background Prospective national registries examining the incidence and aetiology of sports-related sudden cardiac death (SrSCD) not only in competitive athletes but also in recreational sports participants are uncommon. In May 2012, a prospective registry on SrSCD was installed to examine the incidence and particularly the aetiology of such events in the general population in Germany. Methods The registry consists of a web-based platform to record SrSCD cases. Media-monitoring and cooperation with 15 institutes of forensic medicine complemented the search. SrSCD was defined as death occurring during sports activity or up to 1 hour after its cessation, regardless of successful resuscitation. We included subjects at all levels of competition as well as recreational athletes. Results After 30 months of observation, 144 SrSCDs were recorded (mean age 46.8 ± 16.2 years). The overall incidence was 1.2–1.5/million/year, with 97% being male. Most of the cases occurred in the context of non-elite competitive or recreational sports. Football and running were the most common disciplines. In subjects ≤35 years, myocarditis prevailed, whereas in athletes ≥35 years, CAD predominated by far. Few cardiomyopathies were observed. Conclusions In Germany, the largest proportion of SrSCDs occurs in middle-aged men during recreational sports or non-elite competitive sports. The distribution of cardiac diseases responsible for SrSCD seems to vary among European countries. Our findings may indicate the need for a larger focus on myocarditis prevention in the young as well as widening the screening scope to younger athletes below the ‘elite’ level and to senior athletes. PMID:26130495

Histophilosis as a Natural Disease.

PubMed

O'Toole, D; Sondgeroth, K S

2016-01-01

Histophilus somni is responsible for sporadic disease worldwide in cattle and, to a lesser extent, in small ruminants, bighorn sheep (Ovis canadensis), and North American bison (Bison bison). The importance of H. somni diseases can be attributed to improved clinical and laboratory recognition, combined with the growth in intensive management practices for cattle. Although outbreaks of bovine histophilosis can occur year-round, in northern and southern hemispheres, it is most frequent in late fall and early winter. Weather, stress, dietary changes, and comingling of cattle are likely to be major triggers for outbreaks. The most frequent clinical expressions of histophilosis include undifferentiated fever, fibrinosuppurative pneumonia, encephalitis-leptomeningitis, necrotizing myocarditis, and diffuse pleuritis. Neurological disease occurs either as thrombotic meningoencephalitis (TME) or as suppurative meningitis with ventriculitis. Acute myocarditis is characteristically necrotizing and generally involves one or both papillary muscles in the left ventricular myocardium. Biofilm-like aggregates of bacteria occur in capillaries and veins in myocardium, in the central nervous system, and on endocardial surfaces. H. somni is a component of bovine respiratory disease (BRD) complex. In our experience, it is most commonly diagnosed in subacute-to-chronic polymicrobial pulmonary infections in combination with Mannheimia haemolytica, Trueperella pyogenes, Pasteurella multocida, or Mycoplasma bovis. Other, less common forms of H. somni disease present as polyarthritis/tenosynovitis, abortion with placentitis and fetal septicemia, epididymitis-orchitis, and ocular infections. It is likely that H. somni is under-recognized clinically and diagnostically. Most state and provincial laboratories in North America rely on bacterial isolation to confirm infection. The use of more sensitive detection methods on field cases of histophilosis will help resolve the pathogenesis of H. somni in natural outbreaks, and whether the disease is as common elsewhere as it is in Canada.

Data from a nationwide registry on sports-related sudden cardiac deaths in Germany.

PubMed

Bohm, Philipp; Scharhag, Jürgen; Meyer, Tim

2016-04-01

Prospective national registries examining the incidence and aetiology of sports-related sudden cardiac death (SrSCD) not only in competitive athletes but also in recreational sports participants are uncommon. In May 2012, a prospective registry on SrSCD was installed to examine the incidence and particularly the aetiology of such events in the general population in Germany. The registry consists of a web-based platform to record SrSCD cases. Media-monitoring and cooperation with 15 institutes of forensic medicine complemented the search. SrSCD was defined as death occurring during sports activity or up to 1 hour after its cessation, regardless of successful resuscitation. We included subjects at all levels of competition as well as recreational athletes. After 30 months of observation, 144 SrSCDs were recorded (mean age 46.8 ± 16.2 years). The overall incidence was 1.2-1.5/million/year, with 97% being male. Most of the cases occurred in the context of non-elite competitive or recreational sports. Football and running were the most common disciplines. In subjects ≤35 years, myocarditis prevailed, whereas in athletes ≥35 years, CAD predominated by far. Few cardiomyopathies were observed. In Germany, the largest proportion of SrSCDs occurs in middle-aged men during recreational sports or non-elite competitive sports. The distribution of cardiac diseases responsible for SrSCD seems to vary among European countries. Our findings may indicate the need for a larger focus on myocarditis prevention in the young as well as widening the screening scope to younger athletes below the 'elite' level and to senior athletes. © The European Society of Cardiology 2015.

Assessment of acute myocarditis by cardiac magnetic resonance imaging: Comparison of qualitative and quantitative analysis methods.

PubMed

Imbriaco, Massimo; Nappi, Carmela; Puglia, Marta; De Giorgi, Marco; Dell'Aversana, Serena; Cuocolo, Renato; Ponsiglione, Andrea; De Giorgi, Igino; Polito, Maria Vincenza; Klain, Michele; Piscione, Federico; Pace, Leonardo; Cuocolo, Alberto

2017-10-26

To compare cardiac magnetic resonance (CMR) qualitative and quantitative analysis methods for the noninvasive assessment of myocardial inflammation in patients with suspected acute myocarditis (AM). A total of 61 patients with suspected AM underwent coronary angiography and CMR. Qualitative analysis was performed applying Lake-Louise Criteria (LLC), followed by quantitative analysis based on the evaluation of edema ratio (ER) and global relative enhancement (RE). Diagnostic performance was assessed for each method by measuring the area under the curves (AUC) of the receiver operating characteristic analyses. The final diagnosis of AM was based on symptoms and signs suggestive of cardiac disease, evidence of myocardial injury as defined by electrocardiogram changes, elevated troponin I, exclusion of coronary artery disease by coronary angiography, and clinical and echocardiographic follow-up at 3 months after admission to the chest pain unit. In all patients, coronary angiography did not show significant coronary artery stenosis. Troponin I levels and creatine kinase were higher in patients with AM compared to those without (both P < .001). There were no significant differences among LLC, T2-weighted short inversion time inversion recovery (STIR) sequences, early (EGE), and late (LGE) gadolinium-enhancement sequences for diagnosis of AM. The AUC for qualitative (T2-weighted STIR 0.92, EGE 0.87 and LGE 0.88) and quantitative (ER 0.89 and global RE 0.80) analyses were also similar. Qualitative and quantitative CMR analysis methods show similar diagnostic accuracy for the diagnosis of AM. These findings suggest that a simplified approach using a shortened CMR protocol including only T2-weighted STIR sequences might be useful to rule out AM in patients with acute coronary syndrome and normal coronary angiography.

Myocardial infarction triggers chronic cardiac autoimmunity in type 1 diabetes.

PubMed

Gottumukkala, Raju V S R K; Lv, HuiJuan; Cornivelli, Lizbeth; Wagers, Amy J; Kwong, Raymond Y; Bronson, Roderick; Stewart, Garrick C; Schulze, P Christian; Chutkow, William; Wolpert, Howard A; Lee, Richard T; Lipes, Myra A

2012-06-13

Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality after myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert "adjuvant effects" and induce pathological responses in autoimmune-prone T1D hosts. Here, we show that experimental MI in nonobese diabetic mice, but not in control C57BL/6 mice, results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac autoantibody production, and T helper type 1 effector cell responses against cardiac (α-)myosin. PIA was prevented by inducing tolerance to α-myosin, demonstrating that immune responses to cardiac myosin are essential for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and nondiabetic patients with myocarditis, which were absent in post-MI type 2 diabetic patients, and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D and highlight a role for antigen-specific immunointervention to selectively block this pathway.

Post-mortem findings in southern right whales Eubalaena australis at Península Valdés, Argentina, 2003-2012.

PubMed

McAloose, Denise; Rago, M Virginia; Di Martino, Matías; Chirife, Andrea; Olson, Sarah H; Beltramino, Lucas; Pozzi, Luciana M; Musmeci, Luciana; La Sala, Luciano; Mohamed, Nadia; Sala, Juan Emilio; Bandieri, Lucas; Andrejuk, Julian; Tomaszewicz, Ania; Seimon, Tracie; Sironi, Mariano; Samartino, Luis E; Rowntree, Victoria; Uhart, Marcela M

2016-04-12

Between 2003 and 2012, 605 southern right whales (SRW; Eubalaena australis) were found dead along the shores of Península Valdés (PV), Argentina. These deaths included alarmingly high annual losses between 2007 and 2012, a peak number of deaths (116) in 2012, and a significant number of deaths across years in calves-of-the-year (544 of 605 [89.9%]; average = 60.4 yr(-1)). Post-mortem examination and pathogen testing were performed on 212 whales; 208 (98.1%) were calves-of-the-year and 48.0% of these were newborns or neonates. A known or probable cause of death was established in only a small number (6.6%) of cases. These included ship strike in a juvenile and blunt trauma or lacerations (n = 5), pneumonia (n = 4), myocarditis (n = 2), meningitis (n = 1), or myocarditis and meningitis (n = 1) in calves. Ante-mortem gull parasitism was the most common gross finding. It was associated with systemic disease in a single 1-2 mo old calf. Immunohistochemical labeling for canine distemper virus, Toxoplasma gondii and Brucella spp., and PCR for cetacean morbillivirus (CeMV), influenza A, and apicomplexan protozoa were negative on formalin-fixed, paraffin-embedded lung and brain samples from a subset of whales; PCR for Brucella spp. was positive in a newborn/neonate with pneumonia. Skin samples from whales with gull parasitism were PCR negative for CeMV, poxvirus, and papillomavirus. This is the first long-term study to investigate and summarize notable post-mortem findings in the PV SRW population. Consistent, significant findings within or between years to explain the majority of deaths and those in high-mortality years remain to be identified.

Identification of a Lactate-Quinone Oxidoreductase in Staphylococcus aureus that is Essential for Virulence

PubMed Central

Fuller, James R.; Vitko, Nicholas P.; Perkowski, Ellen F.; Scott, Eric; Khatri, Dal; Spontak, Jeffrey S.; Thurlow, Lance R.; Richardson, Anthony R.

2011-01-01

Staphylococcus aureus is an important human pathogen commonly infecting nearly every host tissue. The ability of S. aureus to resist innate immunity is critical to its success as a pathogen, including its propensity to grow in the presence of host nitric oxide (NO·). Upon exogenous NO· exposure, S. aureus immediately excretes copious amounts of L-lactate to maintain redox balance. However, after prolonged NO·-exposure, S. aureus reassimilates L-lactate specifically and in this work, we identify the enzyme responsible for this L-lactate-consumption as a L-lactate-quinone oxidoreductase (Lqo, SACOL2623). Originally annotated as Mqo2 and thought to oxidize malate, we show that this enzyme exhibits no affinity for malate but reacts specifically with L-lactate (KM = ∼330 μM). In addition to its requirement for reassimilation of L-lactate during NO·-stress, Lqo is also critical to respiratory growth on L-lactate as a sole carbon source. Moreover, Δlqo mutants exhibit attenuation in a murine model of sepsis, particularly in their ability to cause myocarditis. Interestingly, this cardiac-specific attenuation is completely abrogated in mice unable to synthesize inflammatory NO· (iNOS−/−). We demonstrate that S. aureus NO·-resistance is highly dependent on the availability of a glycolytic carbon sources. However, S. aureus can utilize the combination of peptides and L-lactate as carbon sources during NO·-stress in an Lqo-dependent fashion. Murine cardiac tissue has markedly high levels of L-lactate in comparison to renal or hepatic tissue consistent with the NO·-dependent requirement for Lqo in S. aureus myocarditis. Thus, Lqo provides S. aureus with yet another means of replicating in the presence of host NO·. PMID:22919585

Coxsackievirus B3 induces the formation of autophagosomes in cardiac fibroblasts both in vitro and in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhai, Xia, E-mail: zhai_xia_cool@126.com; Qin, Ying, E-mail: qinyinggaofeng@163.com; Chen, Yang, E-mail: cy_hmu@126.com

Coxsackievirus group B (CVB) is one of the common pathogens that cause myocarditis and cardiomyopathy. Evidence has shown that CVB replication in cardiomyocytes is responsible for the damage and loss of cardiac muscle and the dysfunction of the heart. However, it remains largely undefined how CVB would directly impact cardiac fibroblasts, the most abundant cells in human heart. In this study, cardiac fibroblasts were isolated from Balb/c mice and infected with CVB type 3 (CVB3). Increased double-membraned, autophagosome-like vesicles in the CVB3-infected cardiac fibroblasts were observed with electron microscope. Punctate distribution of LC3 and increased level of LC3-II were alsomore » detected in the infected cardiac fibroblasts. Furthermore, we observed that the expression of pro-inflammatory cytokines, IL-6 and TNF-α, was increased in the CVB3-infected cardiac fibroblasts, while suppressed autophagy by 3-MA and Atg7-siRNA inhibited cytokine expression. Consistent with the in vitro findings, increased formation of autophagosomes was observed in the cardiac fibroblasts of Balb/c mice infected with CVB3. In conclusion, our data demonstrated that cardiac fibroblasts respond to CVB3 infection with the formation of autophagosomes and the release of the pro-inflammatory cytokines. These results suggest that the autophagic response of cardiac fibroblasts may play a role in the pathogenesis of myocarditis caused by CVB3 infection. - Highlights: • CVB3 replication induced autophagosome assembly in primary cardiac fibroblasts. • Both IL-6 and TNF-α in cardiac fibroblasts infected by CVB3 were increased. • IL-6 and TNF-α were reduced in cardiac fibroblasts when autophagy was inhibited. • Autophagosome assembly in cardiac fibroblasts of CVB-infected mice was increased.« less

Heart Transplant in Patients with Predominantly Rheumatic Valvular Heart Disease.

PubMed

Rosa, Vitor E E; Lopes, Antonio S S A; Accorsi, Tarso A D; Fernandes, Joao Ricardo C; Spina, Guilherme S; Sampaio, Roney O; Bacal, Fernando; Tarasoutchi, Flavio

2015-09-01

International records indicate that only 2.6% of patients with heart transplants have valvular heart disease. The study aim was to evaluate the epidemiological and clinical profile of patients with valvular heart disease undergoing heart transplantation. Between 1985 and 2013, a total of 569 heart transplants was performed at the authors' institution. Twenty patients (13 men, seven women; mean age 39.5 +/- 15.2 years) underwent heart transplant due to structural (primary) valvular disease. Analyses were made of the patients' clinical profile, laboratory data, echocardiographic and histopathological data, and mortality and rejection. Of the patients, 18 (90%) had a rheumatic etiology, with 85% having undergone previous valve surgery (45% had one or more operations), and 95% with a normal functioning valve prosthesis at the time of transplantation. Atrial fibrillation was present in seven patients (35%), while nine (45%) were in NYHA functional class IV and eight (40%) in class III. The indication for cardiac transplantation was refractory heart failure in seven patients (35%) and persistent NYHA class III/IV in ten (50%). The mean left ventricular ejection fraction (LVEF) was 26.6 +/- 7.9%. The one-year mortality was 20%. Histological examination of the recipients' hearts showed five (27.7%) to have reactivated rheumatic myocarditis without prior diagnosis at the time of transplantation. Univariate analysis showed that age, gender, LVEF, rheumatic activity and rejection were not associated with mortality at one year. Among the present patient cohort, rheumatic heart disease was the leading cause of heart transplantation, and a significant proportion of these patients had reactivated myocarditis diagnosed in the histological analyses. Thus, it appears valid to investigate the existence of rheumatic activity, especially in valvular cardiomyopathy with severe systolic dysfunction before transplantation.

Fatal Lyme carditis and endodermal heterotopia of the atrioventricular node.

PubMed Central

Cary, N. R.; Fox, B.; Wright, D. J.; Cutler, S. J.; Shapiro, L. M.; Grace, A. A.

1990-01-01

A fatal case of Lyme carditis occurring in a Suffolk farmworker is reported. Post-mortem examination of the heart showed pericarditis, focal myocarditis and prominent endocardial and interstitial fibrosis. The additional finding of endodermal heterotopia ('mesothelioma') of the atrioventricular node raises the possibility that this could also be related to Lyme infection and account for the relatively frequent occurrence of atrioventricular block in this condition. Lyme disease should always be considered in a case of atrioventricular block, particularly in a young patient from a rural area. The heart block tends to improve and therefore only temporary pacing may be required. Images Figure 1 Figure 2 Figure 3 PMID:2349186

Sudden infant death syndrome caused by poliomyelitis.

PubMed

Dunne, J W; Harper, C G; Hilton, J M

1984-07-01

Most seemingly well infants who die suddenly and unexpectedly have no adequate cause of death found on thorough postmortem examination. Respiratory and enteric viruses are often present, especially in the upper respiratory tract, but the infective process seems, of itself, insufficient to cause death. In the remainder of the cases, a variety of lesions will be discovered, including viral myocarditis, bronchiolitis, and sepsis. We report a case of sudden and unexpected death in a 5-week-old male infant due to acute anterior poliomyelitis. This case illustrates the importance of a thorough postmortem examination, including histologic studies of the brain stem and spinal cord in cases of sudden infant death syndrome.

[Phaeochromocytoma as an unusual aetiology of cardiogenic shock].

PubMed

Ouchikhe, A; Lehoux, P; Gringore, A; Renouf, P; Deredec, R; Tasle, M; Massetti, M; Khayat, A; Saloux, E; Grollier, G; Samama, G; Gérard, J-L

2006-01-01

The authors reported a case involving a young patient with a cardiogenic shock associated to an acute pulmonary oedema. According to the seriousness of the shock, an external ventricular assist device (VAD) was initially inserted and replaced thereafter because of the cardiovascular instability, by an external pneumatic biventricular assist device. A cardiogenic shock induced by an acute adrenergic myocarditis due to a phaeochromocytoma was diagnosed. The patient was weaned from the VAD on day 84 and was scheduled for elective surgery of the phaeochromocytoma on day 93. The authors discussed the time of the surgery according to the anticoagulation therapy necessary to the VAD and the necessary caution taken if a cardiogenic shock appeared around surgery.

Cardiac tamponade leading to the diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a case report and review of the literature.

PubMed

Yano, Toshiyuki; Ishimura, Shutaro; Furukawa, Tetsuaki; Koyama, Masayuki; Tanaka, Marenao; Shimoshige, Shinya; Hashimoto, Akiyoshi; Miura, Tetsuji

2015-11-01

Eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called Churg-Strauss syndrome, is a necrotizing systemic vasculitis of unknown cause accompanied by prominent eosinophilia. Cardiovascular complications, including eosinophilic myocarditis, are a major cause of mortality in this disorder. Acute pericarditis with slight pericardial effusion is a typical manifestation in EGPA, though hemodynamically significant pericardial effusion has been reported in a few cases. We report a case that initially presented with isolated cardiac tamponade, which was followed by systemic manifestations of EGPA over 3 weeks. Including the present case, previous EGPA cases with cardiac tamponade are reviewed to delineate its clinical characteristics.

The role of the Intra‐aortic balloon pump in supporting children with acute cardiac failure

PubMed Central

Collison, Sathiakar Paul; Dagar, Kulbhusan Singh

2007-01-01

Acute heart failure occurs in children following the operative correction of a congenital anomaly, as an acute change in a child with a congenital anomaly, or in a structurally normal heart with acute myocarditis. Acute heart failure in children justifies aggressive treatment because of the high potential for complete recovery. The options for providing mechanical support to the failing heart in a child include extracorporeal membrane oxygenation, left ventricular assist devices and the use of the intra‐aortic balloon pump (IABP). The principles of intra‐aortic balloon pump usage are described, and the literature regarding the indications and outcome of its use in children is reviewed. PMID:17488858

Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.

PubMed

Merlo, Marco; Anzini, Marco; Bussani, Rossana; Artico, Jessica; Barbati, Giulia; Stolfo, Davide; Gigli, Marta; Muça, Matilda; Naso, Paola; Ramani, Federica; Di Lenarda, Andrea; Pinamonti, Bruno; Sinagra, Gianfranco

2016-09-15

Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping tissue inhomogeneity in acute myocarditis: a novel analytical approach to quantitative myocardial edema imaging by T2-mapping.

PubMed

Baeßler, Bettina; Schaarschmidt, Frank; Dick, Anastasia; Stehning, Christian; Schnackenburg, Bernhard; Michels, Guido; Maintz, David; Bunck, Alexander C

2015-12-23

The purpose of the present study was to investigate the diagnostic value of T2-mapping in acute myocarditis (ACM) and to define cut-off values for edema detection. Cardiovascular magnetic resonance (CMR) data of 31 patients with ACM were retrospectively analyzed. 30 healthy volunteers (HV) served as a control. Additionally to the routine CMR protocol, T2-mapping data were acquired at 1.5 T using a breathhold Gradient-Spin-Echo T2-mapping sequence in six short axis slices. T2-maps were segmented according to the 16-segments AHA-model and segmental T2 values as well as the segmental pixel-standard deviation (SD) were analyzed. Mean differences of global myocardial T2 or pixel-SD between HV and ACM patients were only small, lying in the normal range of HV. In contrast, variation of segmental T2 values and pixel-SD was much larger in ACM patients compared to HV. In random forests and multiple logistic regression analyses, the combination of the highest segmental T2 value within each patient (maxT2) and the mean absolute deviation (MAD) of log-transformed pixel-SD (madSD) over all 16 segments within each patient proved to be the best discriminators between HV and ACM patients with an AUC of 0.85 in ROC-analysis. In classification trees, a combined cut-off of 0.22 for madSD and of 68 ms for maxT2 resulted in 83% specificity and 81% sensitivity for detection of ACM. The proposed cut-off values for maxT2 and madSD in the setting of ACM allow edema detection with high sensitivity and specificity and therefore have the potential to overcome the hurdles of T2-mapping for its integration into clinical routine.

Critically Ill Children During the 2009–2010 Influenza Pandemic in the United States

PubMed Central

Vaughn, Frances; Sullivan, Ryan; Rubinson, Lewis; Thompson, B. Taylor; Yoon, Grace; Smoot, Elizabeth; Rice, Todd W.; Loftis, Laura L.; Helfaer, Mark; Doctor, Allan; Paden, Matthew; Flori, Heidi; Babbitt, Christopher; Graciano, Ana Lia; Gedeit, Rainer; Sanders, Ronald C.; Giuliano, John S.; Zimmerman, Jerry; Uyeki, Timothy M.

2011-01-01

BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had ≥1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1–20.6]; P < .0001) remained a mortality risk factor. CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors. PMID:22065262

A Systematic Review of Mortality from Untreated Scrub Typhus (Orientia tsutsugamushi).

PubMed

Taylor, Andrew J; Paris, Daniel H; Newton, Paul N

2015-01-01

Scrub typhus, a bacterial infection caused by Orientia tsutsugamushi, is increasingly recognized as an important cause of fever in Asia, with an estimated one million infections occurring each year. Limited access to health care and the disease's non-specific symptoms mean that many patients are undiagnosed and untreated, but the mortality from untreated scrub typhus is unknown. This review systematically summarizes the literature on the untreated mortality from scrub typhus and disease outcomes. A literature search was performed to identify patient series containing untreated patients. Patients were included if they were symptomatic and had a clinical or laboratory diagnosis of scrub typhus and excluded if they were treated with antibiotics. The primary outcome was mortality from untreated scrub typhus and secondary outcomes were total days of fever, clinical symptoms, and laboratory results. A total of 76 studies containing 89 patient series and 19,644 patients were included in the final analysis. The median mortality of all patient series was 6.0% with a wide range (min-max) of 0-70%. Many studies used clinical diagnosis alone and had incomplete data on secondary outcomes. Mortality varied by location and increased with age and in patients with myocarditis, delirium, pneumonitis, or signs of hemorrhage, but not according to sex or the presence of an eschar or meningitis. Duration of fever was shown to be long (median 14.4 days Range (9-19)). Results show that the untreated mortality from scrub typhus appears lower than previously reported estimates. More data are required to clarify mortality according to location and host factors, clinical syndromes including myocarditis and central nervous system disease, and in vulnerable mother-child populations. Increased surveillance and improved access to diagnostic tests are required to accurately estimate the untreated mortality of scrub typhus. This information would facilitate reliable quantification of DALYs and guide empirical treatment strategies.

Nitric oxide synthase 2 is required for conversion of pro-fibrogenic inflammatory CD133(+) progenitors into F4/80(+) macrophages in experimental autoimmune myocarditis.

PubMed

Blyszczuk, Przemyslaw; Berthonneche, Corrine; Behnke, Silvia; Glönkler, Marcel; Moch, Holger; Pedrazzini, Thierry; Lüscher, Thomas F; Eriksson, Urs; Kania, Gabriela

2013-02-01

Experimental autoimmune myocarditis (EAM) model mirrors important mechanisms of inflammatory dilated cardiomyopathy (iDCM). In EAM, inflammatory CD133(+) progenitors are a major cellular source of cardiac myofibroblasts in the post-inflammatory myocardium. We hypothesized that exogenous delivery of macrophage-colony-stimulating factor (M-CSF) can stimulate macrophage lineage differentiation of inflammatory progenitors and, therefore, prevent their naturally occurring myofibroblast fate in EAM. EAM was induced in wild-type (BALB/c) and nitric oxide synthase 2-deficient (Nos2(-/-)) mice and CD133(+) progenitors were isolated from inflamed hearts. In vitro, M-CSF converted inflammatory CD133(+) progenitors into nitric oxide-producing F4/80(+) macrophages and prevented transforming growth factor-β-mediated myofibroblast differentiation. Importantly, only a subset of heart-infiltrating CD133(+) progenitors expresses macrophage-specific antigen F4/80 in EAM. These CD133(+)/F4/80(hi) cells show impaired myofibrogenic potential compared with CD133(+)/F4/80(-) cells. M-CSF treatment of wild-type mice with EAM at the peak of disease markedly increased CD133(+)/F4/80(hi) cells in the myocardium, and CD133(+) progenitors isolated from M-CSF-treated mice failed to differentiate into myofibroblasts. In contrast, M-CSF was not effective in converting CD133(+) progenitors from inflamed hearts of Nos2(-/-) mice into macrophages, and M-CSF treatment did not result in increased CD133(+)/F4/80(hi) cell population in hearts of Nos2(-/-) mice. Accordingly, M-CSF prevented post-inflammatory fibrosis and left ventricular dysfunction in wild-type but not in Nos2(-/-) mice. Active and NOS2-dependent induction of macrophage lineage differentiation abrogates the myofibrogenic potential of heart-infiltrating CD133(+) progenitors. Modulating the in vivo differentiation fate of specific progenitors might become a novel approach for the treatment of inflammatory heart diseases.

Effects of functional feeds on the lipid composition, transcriptomic responses and pathology in heart of Atlantic salmon (Salmo salar L.) before and after experimental challenge with Piscine Myocarditis Virus (PMCV).

PubMed

Martinez-Rubio, Laura; Evensen, Øystein; Krasnov, Aleksei; Jørgensen, Sven Martin; Wadsworth, Simon; Ruohonen, Kari; Vecino, Jose L G; Tocher, Douglas R

2014-06-11

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of Atlantic salmon (Salmo salar) recently associated with a double-stranded RNA virus, Piscine Myocarditis Virus (PMCV). The disease has been diagnosed in 75-85 farms in Norway each year over the last decade resulting in annual economic losses estimated at up to €9 million. Recently, we demonstrated that functional feeds led to a milder inflammatory response and reduced severity of heart lesions in salmon experimentally infected with Atlantic salmon reovirus, the causal agent of heart and skeletal muscle inflammation (HSMI). In the present study we employed a similar strategy to investigate the effects of functional feeds, with reduced lipid content and increased eicosapentaenoic acid levels, in controlling CMS in salmon after experimental infection with PMCV. Hepatic steatosis associated with CMS was significantly reduced over the time course of the infection in fish fed the functional feeds. Significant differences in immune and inflammatory responses and pathology in heart tissue were found in fish fed the different dietary treatments over the course of the infection. Specifically, fish fed the functional feeds showed a milder and delayed inflammatory response and, consequently, less severity of heart lesions at earlier and later stages after infection with PMCV. Decreasing levels of phosphatidylinositol in cell membranes combined with the increased expression of genes related with T-cell signalling pathways revealed new interactions between dietary lipid composition and the immune response in fish during viral infection. Dietary histidine supplementation did not significantly affect immune responses or levels of heart lesions. Combined with the previous findings on HSMI, the results of the present study highlight the potential role of clinical nutrition in controlling inflammatory diseases in Atlantic salmon. In particular, dietary lipid content and fatty acid composition may have important immune-modulatory effects in Atlantic salmon that could be potentially beneficial in fish balancing the immune and tissue responses to viral infections.

Sympathetic nerve blocks promote anti-inflammatory response by activating the JAK2-STAT3-mediated signaling cascade in rat myocarditis models: A novel mechanism with clinical implications.

PubMed

Park, Hyelim; Park, Hyewon; Mun, Dasom; Kim, Michael; Pak, Hui-Nam; Lee, Moon-Hyoung; Joung, Boyoung

2018-05-01

Left stellectomy has become an important therapeutic option for patients with potentially fatal arrhythmias. However, the antiarrhythmic mechanism of left stellectomy is not well known. The cholinergic anti-inflammatory pathway (CAIP) is a complex immune mechanism that regulates peripheral inflammatory responses. The purpose of this study was to evaluate the effect of left stellectomy on CAIP using rat experimental autoimmune myocarditis (EAM) models. EAM was produced by injecting 2 mg of porcine cardiac myosin into the footpads of rats. Left stellectomy was performed before EAM induction. We evaluated the effect of left stellectomy on arrhythmic events, survival, inflammation, and CAIP in rats without and with EAM. Left stellectomy prevented arrhythmia and improved survival in EAM rats. Left stellectomy decreased the levels of tumor necrosis factor α, interleukin 6, and high mobility group box 1 (P < .05 vs EAM) in serum and heart tissues from EAM rats. In heart rate variability analysis, high-frequency peaks of the power spectrum densities, reflecting parasympathetic cardiovagal tone, were significantly decreased in EAM rats, but increased after left stellectomy. The ratios of phosphorylated STAT3/STAT3 (signal transducer and activator of transcription 3) and phosphorylated JAK2/JAK2 (Janus kinase 2) decreased in cell lysates of the spleen, liver, and heart in EAM rats. However, the same ratios significantly increased after left stellectomy. Nuclear factor κB in cell lysates of the spleen, liver, and heart increased in EAM rats, but decreased after left stellectomy. In EAM models, left stellectomy increased survival of the rats while showing antiarrhythmic effects with reduced inflammation via activation of the JAK2-STAT3-mediated signaling cascade. Our findings suggest an exciting opportunity to develop new and novel therapeutics to attenuate cardiac inflammation. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

[Influenza infection in intensive cardiac care unit patients].

PubMed

Ciuraszkiewicz, Katrzyna; Sielski, Janusz; Janion-Sadowska, Agnieszka; Stern, Agnieszka; Zychowicz, Joanna; Kaziród-Wolski, Karol; Paluchowski, Marian

2014-03-01

Infection with influenza type A virus may cause serious cardiovascular complications, such as myocarditis, heart failure, acute myocardial infarction. Also infection with influenza type AH1N1 may contribute to aggravation of cardiac disorders, i.e. acute coronary syndrome, heart failure, cardiogenic shock, severe ventricular arrythmias. One of the most fatal complication of influenza is pneumonia leading to acute respiratory insufficiency requiring artifitial ventilation. Symptoms of respiratory tract infections durnig influenza epidemy should always be treated with a high index of suspicion. Early diagnosis and adequate antiviral treatment may prevent those complications. A series of four cases of patients hospitalised in intensive cardiac care unit due to suspected cardiac dyspnea and finally diagnosed as a cardiac disease complicated by influenza pneumonia is presented.

Fatal toxoplasmosis in a vinaceous Amazon parrot (Amazona vinacea).

PubMed

Ferreira, Francisco Carlos; Donatti, Rogerio Venâncio; Marques, Marcus Vinícius Romero; Ecco, Roselene; Preis, Ingred Sales; Shivaprasad, H L; Vilela, Daniel Ambrózio da Rocha; Martins, Nelson Rodrigo da Silva

2012-12-01

Toxoplasmosis was diagnosed in a vinaceous Amazon parrot based on histopathology and immunohistochemistry. The bird was prostrate on the bottom of the cage and died. Necropsy revealed edema and congestion of the lungs, cloudy air sacs, and mild hepatomegaly. Histopathology revealed severe pulmonary congestion and edema and interstitial mononuclear cell inflammation associated with many cysts containing bradyzoites of Toxoplasma gondii scattered throughout. The heart had mild multifocal lymphocytic myocarditis and free tachyzoites in the muscle fibers, and the kidneys had mild interstitial nephritis and a few cysts containing bradyzoites of T. gondii. Immunohistochemistry was negative for Sarcocystis falcatula and Neospora caninum and confirmed the protozoa as T. gondii. This is the first description of T. gondii in an endangered species ofa Brazilian psittacine.

Ultrasound microscope: the new field in ultrasound diagnostics

NASA Astrophysics Data System (ADS)

Novyc'kyy, Victor V.; Lushchyk, Ulyana B.

2001-06-01

A device which is a new stage in the development of medical equipment has been developed. The device works as an ultrasound microscope in vivo and provides 4 up to 32 colored histological image. It gives possibility to estimate tissue acoustic density with the help of 4 up to 32 gradation coloring different tissues and enables tissue microcirculation visualization. With the help of the device a doctor can objectify fatty hepatitis and cirrhosis, edema of different organs and tissues as well as microcirculation in organs and tissues (e.g. muscles, myocard and bone system). New promising applications of ultrasound systems in diagnostics and for choosing individual treatment tactics, with pathogenesis being taken into account, may be developed with the help of the device.

Hemophagocytic Syndrome Complicated with Dermatomyositis Controlled Successfully with Infliximab and Conventional Therapies

PubMed Central

Komiya, Yoji; Saito, Tetsuya; Mizoguchi, Fumitaka; Kohsaka, Hitoshi

2017-01-01

A 57-year-old woman was admitted to our hospital because of a high fever, anemia, and hyperferritinemia. Since a bone marrow examination revealed hemophagocytosis, she was diagnosed with hemophagocytic syndrome (HPS). During treatment of HPS, a heliotrope rash and Gottron's sign appeared with elevated levels of serum aldolase. She also developed heart failure. She was diagnosed with dermatomyositis (DM) and associated myocarditis. Although the administration of glucocorticoids, calcineurin inhibitors, intravenous immunoglobulins, and etoposide ameliorated the clinical findings of DM and cytopenia, the fever and hyperferritinemia remained. The addition of infliximab to glucocorticoids and tacrolimus improved the fever and hyperferritinemia and enabled a reduction in the dose of prednisolone without relapse of the diseases. PMID:29199203

Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection.

PubMed

Fukuda, Yutaka; Momoi, Nobuo; Akaihata, Mitsuko; Nagasawa, Katsutoshi; Mitomo, Masaki; Aoyagi, Yoshimichi; Endoh, Kisei; Hosoya, Mitsuaki

2015-08-01

Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis-like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11-year-old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists. © 2015 Japan Pediatric Society.

Myopéricardite aiguë simulant un infarctus du myocarde: à propos d'une observation et revue de la littérature

PubMed Central

Bouzerda, Abdelmajid

2015-01-01

Le diagnostic de myopéricardite aiguë est difficile surtout quand la présentation clinique mime un syndrome coronaire aiguë. Nous rapportons l'observation d'un patient âgé de 40 ans admis pour un syndrome coronarien aiguë ST+ chez qui la coronarographie réalisée en urgence montre un réseau coronaire angio-graphiquement sain. L'imagerie par résonance magnétique (IRM) permettra d'affirmer le diagnostic d'une myopéricardite. Cette observation confirme le rôle primordial de l'IRM cardiaque chez les patients présentant une suspicion clinique de myocardite aiguë ou un tableau de SCA à coronaire saines. PMID:26491513

[Sepsis, cardiomyopathy and human immunodeficiency virus infection: presentation of a case].

PubMed

Llagunes, J; Arastey, S; Cobo Del Prado, I; Carmona, P; Peña, J J; Mínguez, C

2014-04-01

Sepsis in patients with human immunodeficiency virus (HIV) may be associated with the appearance of cardiac dysfunction. This is a challenge, both when making the differential diagnosis and determining the proper treatment, as there are numerous risk factors: Myocarditis due to the HIV itself, the presence or absence of highly active antiretroviral therapy, toxic substances, and cardiomyopathy associated with sepsis. The diagnostic and therapeutic approach to an HIV positive patient with septic shock and cardiac dysfunction is described, as well as a brief review of the different causes of cardiomyopathy which may affect this group of patients is also presented. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Orally-transmitted Chagas disease.

PubMed

Filigheddu, Maria Teresa; Górgolas, Miguel; Ramos, José Manuel

2017-02-09

Chagas disease is a zoonosis caused by protozoan parasite Trypanosoma cruzi, which is most frequently associated with a vectorial transmission. However, in recent years we have observed a significant increase in the oral transmission of the disease, associated mainly with the consumption of drinks made from fruit or other vegetables contaminated with triatomine faeces or secretions from infected mammals. After a latency period of 3 to 22 days after ingestion, the oral infection is characterized by more severe manifestations than those associated with vectorial transmission: prolonged fever, acute myocarditis with heart failure and, in some cases, meningoencephalitis. Mortality can reach up to 33% of those infected. The aim of this paper is to review this matter and to promote prevention practices. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Fulminant myocardial bleeding: another clinical course of vascular Ehlers-Danlos Syndrome.

PubMed

Tokue, Masahide; Hara, Hidehiko; Kurosawa, Kenji; Nakamura, Masato

2017-09-23

Vascular Ehlers-Danlos Syndrome (vEDS) is a dominantly inherited connective tissue disorder characterised by colon rupture and arterial aneurysm, dissection and rupture. A patient was diagnosed with vEDS after a spontaneous colon rupture when he was brought to our institute because of sudden chest pain. An ECG revealed wide regional ST elevation, which was initially suggestive of acute myocarditis. On the second day, haemodynamics suddenly deteriorated because of a rapid accumulation of bloody pericardial effusion, and the patient died. Autopsy revealed an excessive spontaneous myocardial haemorrhage owing to fragility, which suggested an underlying disease-vEDS. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Fulminant endocarditis and disseminated infection caused by carbapenem-resistant Acinetobacter baumannii in a renal-pancreas transplant recipient.

PubMed

Patel, G; Perez, F; Hujer, A M; Rudin, S D; Augustine, J J; Jacobs, G H; Jacobs, M R; Bonomo, R A

2015-04-01

Acinetobacter baumannii is an important cause of healthcare-associated infections, and is particularly problematic among patients who undergo organ transplantation. We describe a case of fulminant sepsis caused by carbapenem-resistant A. baumannii harboring the blaOXA-23 carbapenemase gene and belonging to international clone II. This isolate led to the death of a patient 6 days after simultaneous kidney-pancreas transplantation. Autopsy findings revealed acute mitral valve endocarditis, myocarditis, splenic and renal emboli, peritonitis, and pneumonia. This case highlights the severe nature of certain A. baumannii infections and the vulnerability of transplanted patients to the increasingly intractable "high-risk" clones of multidrug-resistant organisms. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Toxoplasmosis as a travel risk.

PubMed

Sepúlveda-Arias, Juan C; Gómez-Marin, Jorge E; Bobić, Branko; Naranjo-Galvis, Carlos A; Djurković-Djaković, Olgica

2014-01-01

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects more than one third of the global population. Primary infection in immunocompetent individuals is usually asymptomatic; however, different organs can be affected in immunocompromised individuals leading to the development of encephalitis, myocarditis or pneumonitis. The prevalence of infection with Toxoplasma as well as its genetic structure varies geographically and for that reason travel may be considered as a risk factor to acquire the infection. As toxoplasmosis is a foodborne disease, health care providers should give health education on prevention measures to all prospective travelers in order to decrease the risk of infection in endemic areas. This review presents an overview of the infection with T. gondii with some considerations for travelers to and from endemic zones. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular phenotypes of human parvovirus B19 in patients with myocarditis.

PubMed

Bock, C-Thomas; Düchting, Anja; Utta, Friederike; Brunner, Eva; Sy, Bui Tien; Klingel, Karin; Lang, Florian; Gawaz, Meinrad; Felix, Stephan B; Kandolf, Reinhard

2014-04-26

To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy (DCM). Endomyocardial biopsies (EMBs) from 498 B19V-positive patients with myocarditis and DCM were analyzed using molecular methods and functional experiments. EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers. Control tissues were obtained at autopsy from 34 victims of accidents, crime or suicide. Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining. Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction (PCR). For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism (RFLP)-PCR was established. B19V-genotyping was verified by direct DNA-sequencing and sequences were aligned using BLAST and BioEdit software. B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments. Transfection experiments were conducted using human endothelial cells 1. Luciferase reporter assays were performed to determine B19V-replication activity. Statistical analysis and graphical representation were calculated using SPSS and Prism5 software. The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy (iCMP) compared to uninflamed DCM (59.6% vs 35.3%) (P < 0.0001). The detection of B19V-mRNA replication intermediates proved that replication of B19V was present. RFLP-PCR assays showed that B19V-genotype 1 (57.4%) and B19V-genotype 2 (36.7%) were the most prevalent viral genotypes. B19V-genotype 2 was observed more frequently in EMBs with iCMP (65.0%) compared to DCM (35%) (P = 0.049). Although there was no significant difference in gender-specific B19V-loads, women were more frequently infected with B19V-genotype 2 (44.6%) than men (36.0%) (P = 0.0448). Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissue samples and was associated with higher B19V viral load compared to B19V-monoinfected tissue (P = 0.0012). The most frequent coinfecting virus was human herpes virus 6 (HHV6, 16.5%). B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs (P = 0.0033), suggesting that HHV6 had transactivated B19V. In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator. The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP. Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.

Molecular phenotypes of human parvovirus B19 in patients with myocarditis

PubMed Central

Bock, C-Thomas; Düchting, Anja; Utta, Friederike; Brunner, Eva; Sy, Bui Tien; Klingel, Karin; Lang, Florian; Gawaz, Meinrad; Felix, Stephan B; Kandolf, Reinhard

2014-01-01

AIM: To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy (DCM). METHODS: Endomyocardial biopsies (EMBs) from 498 B19V-positive patients with myocarditis and DCM were analyzed using molecular methods and functional experiments. EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers. Control tissues were obtained at autopsy from 34 victims of accidents, crime or suicide. Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining. Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction (PCR). For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism (RFLP)-PCR was established. B19V-genotyping was verified by direct DNA-sequencing and sequences were aligned using BLAST and BioEdit software. B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments. Transfection experiments were conducted using human endothelial cells 1. Luciferase reporter assays were performed to determine B19V-replication activity. Statistical analysis and graphical representation were calculated using SPSS and Prism5 software. RESULTS: The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy (iCMP) compared to uninflamed DCM (59.6% vs 35.3%) (P < 0.0001). The detection of B19V-mRNA replication intermediates proved that replication of B19V was present. RFLP-PCR assays showed that B19V-genotype 1 (57.4%) and B19V-genotype 2 (36.7%) were the most prevalent viral genotypes. B19V-genotype 2 was observed more frequently in EMBs with iCMP (65.0%) compared to DCM (35%) (P = 0.049). Although there was no significant difference in gender-specific B19V-loads, women were more frequently infected with B19V-genotype 2 (44.6%) than men (36.0%) (P = 0.0448). Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissue samples and was associated with higher B19V viral load compared to B19V-monoinfected tissue (P = 0.0012). The most frequent coinfecting virus was human herpes virus 6 (HHV6, 16.5%). B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs (P = 0.0033), suggesting that HHV6 had transactivated B19V. In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator. CONCLUSION: The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP. Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype. PMID:24772258

Toxocariasis-associated cardiac diseases--A systematic review of the literature.

PubMed

Kuenzli, Esther; Neumayr, Andreas; Chaney, Matthew; Blum, Johannes

2016-02-01

Toxocariasis, caused by Toxocara canis or Toxocara catis, is a worldwide occurring parasitic disease, reaching high prevalences especially in tropical and subtropical countries. The clinical presentation can range from asymptomatic seropositivity to life threatenting disease, depending on the organ system involved. Cardiac involvement, one of the possible manifestations of human Toxocara spp. infection, is rarely reported in case reports. As far as we know, no systematic reviews of clinical presentations have been published till now and no clear recommendations regarding the treatment of Toxocara spp. infection involving the heart exist. In a systematic review of the literature, 24 published cases of Toxocara spp. infection involving the heart were identified. The cardiac entities described included myocarditis, pericarditis, and Loeffler's endocarditis. The clinical presentation ranged from asymptomatic or mild disease to life threatening myocarditis/pericarditis with heart failure or cardiac tamponade, leading to death. In most cases, the diagnosis was based on a combination of clinical, laboratory and radiological findings. Only in three of the nine cases in which histological analysis was performed (either pre- or post-mortem), granulomas or remnants of the parasite were detected. In the other six cases, findings were non-specific; the damage of the heart was equally caused by direct invasion of the larvae and by immunological reactions, either caused by the systemic hypereosinophilia or by the presence of the larvae in the tissue. The treatment regimen described mostly consisted of anthelmintic drugs in combination with corticosteroids. Even though dosage and duration of treatment varied widely, ranging from days to months, most patients were treated successfully. Cardiac involvement in Toxocara spp. infection is a rare but potentially life-threatening complication of a very common disease. The therapeutic regimens vary widely especially with regard to the duration of therapy, however, the combination of an anthelmintic drug and a corticosteroid appears to be a valuable option. For the daily clinical work, tissue manifestation by parasites should be considered in cases of unspecific organ manifestations, (i.e. heart, lungs, liver), accompanied by fever and eosinophilia with or without allergic skin rashes. Copyright © 2015 Elsevier B.V. All rights reserved.

Les syndromes coronaires aigus à Dakar: aspects cliniques thérapeutiques et évolutifs

PubMed Central

Mboup, Mouhamed Cherif; Diao, Maboury; Dia, Khadidiatou; Fall, Pape Diadie

2014-01-01

Introduction Ce travail a pour objectifs d’étudier les aspects épidémiologiques et cliniques, les différentes modalités de prise en charge, et l’évolution des syndromes coronaires aigus à Dakar. Méthodes Il s'agit d'une étude prospective concernant une cohorte de patients hospitalisés au niveau des services de cardiologie de l'hôpital Principal de Dakar et de l'hôpital Aristide Le Dantec pour un syndrome coronaire aigu entre le 01 Septembre 2005 et le 31 Août 2006. Résultats Durant la période d’étude, 59 patients avaient présenté à l'admission un syndrome coronaire aigu, soit une prévalence hospitalière de 4,05%. L’âge moyen était de 57,1 ± 3,5 ans. L'indice moyen des facteurs de risque était de 3,56 ± 1,7. Quatre vingt onze pour cent (91%) des patients avaient au moins deux facteurs de risque cardio-vasculaires. Les délais moyens d'arrivée et de prise en charge étaient respectivement de 53,2 ± 21,3 heures et 3,4 ± 1 heures. L'analyse des tracés électrocardiographiques associée au dosage des troponines, avait permis de retenir les diagnostics d'infarctus du myocarde avec sus-décalage persistant du segment ST chez 89,8% patients, d'infarctus du myocarde sans sus-décalage du segment ST chez 5,1% patients, et d'angor instable dans 5,1% des cas. La mortalité hospitalière était de 15,25% et la mortalité à un mois de 18,64%. Conclusion Au Sénégal, les syndromes coronaires aigus sont caractérisés par un âge de survenue relativement jeune chez des patients polyfactoriels et une lourde mortalité. C'est dire tout l'intérêt d'une prévention primaire efficace par la lutte contre les facteurs de risque cardio-vasculaires. PMID:25745533

Mid-term Risk for Subclinical Atherosclerosis and Chronic Myocarditis in Children with Kawasaki Disease and Transient Coronary Abnormalities.

PubMed

Parihar, Mansingh; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar

2017-08-01

There is evidence for premature atherosclerosis and systemic arterial stiffening during follow-up of children with Kawasaki disease (KD) and coronary artery abnormalities (CAA). Moreover, patients with KD may also have subclinical myocardial involvement and inhomogeneous ventricular repolarization. The inhomogeneous ventricular repolarization manifests as increased QT dispersion on electrocardiography. There is a paucity of studies in endothelial dysfunction and QT dispersion in children with KD and transient CAA. Twenty children with KD and transient CAA were studied at least 1 year after resolution of CAA. Mean follow-up period between KD onset and enrolment in the study was 53.7 months. Twenty age and sex-matched controls were enrolled. High-resolution B-mode ultrasonography was used to analyze brachial artery dilatation in response to reactive hyperemia (cases and controls) and sublingual nitroglycerine (cases only). Carotid artery intima-media thickness (cIMT) and stiffness index were calculated. The difference between maximum and minimum QTc intervals on 12 lead electrocardiogram was calculated as QTc dispersion (QTcd). No statistically significant difference was noted in percent flow-mediated dilatation of brachial arteries in response to reactive hyperemia between cases (13.31 ± 10.41%) and controls (12.86 ± 7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was 14.88 ± 12.03%. Mean cIMT was similar in cases (0.036 ± 0.015 cm) and controls (0.035 ± 0.076 cm; p = 0.791). No statistically significant difference between groups was observed in mean QTcd values (0.057 ± 0.018 s vs. 0.059 ± 0.015 s in controls, p = 0.785). No evidence of significant endothelial dysfunction or increased QT dispersion in patients with KD and transient coronary artery abnormalities was found in our cohort when studied at a mean follow-up of 53.7 months. This is reassuring, and indicates that risk of subclinical atherosclerosis and myocarditis in a subset of children with KD and transient coronary artery abnormalities is not significant.

The mitochondrial respiratory chain has a critical role in the antiviral process in Coxsackievirus B3-induced myocarditis.

PubMed

Ebermann, Linda; Wika, Sylwia; Klumpe, Inga; Hammer, Elke; Klingel, Karin; Lassner, Dirk; Völker, Uwe; Erben, Ulrike; Zeichhardt, Heinz; Schultheiss, Heinz-Peter; Dörner, Andrea

2012-01-01

Well-established differences in Coxsackievirus B3 (CVB3) elimination in resistant C57BL/6 and permissive A.SW/SnJ mice provide suitable models for studying the significance of the link between mitochondrial respiratory chain (RC), antioxidative stress components and mitochondrion-related apoptosis in the context of myocardial virus elimination. Distinct myocardial CVB3 titer in C57BL/6 (2.5 ± 1.4 × 10(4) plaque-forming units (p.f.u.)/g tissue) and A.SW/SnJ mice (1.4 ± 0.8 × 10(7) p.f.u./g) were associated with differences in the cardiac mitochondrial function 8 days post infection (p.i.). Infected C57BL/6 mouse hearts disclosed increased complex I (CI) and CIII activity, but restricted CII and normal CIV activity of RC. Reduced expression of the antioxidative catalase was accompanied by elevated lipid peroxidation (LPO), indicating oxidative stress. Intrinsic apoptosis was activated demonstrated by elevated levels of Bax, Bcl-2, caspase 3 and DNA degradation. In contrast, all myocardial RC complex activities were restricted in CVB3-infected A.SW/SnJ mice. The antioxidative system provided sufficient protection against oxidative stress shown by an elevated catalase expression and unaltered LPO. Bax and Bcl-2 levels were unchanged in CVB3-infected A.SW/SnJ mice, while caspase 3 was moderately increased but no DNA degradation was detectable. Correlation analyses including data from the two mouse strains revealed that reduced CVB3 titer correlated with increased CI and CIII activity, oxidative stress as well as active apoptosis during acute myocarditis (MC). C57BL/6 mice completely eliminated CVB3 and inflammation and normalized all intracellular parameters, while A.SW/SnJ mice showed permanently restricted CI activity in chronic MC 90 days p.i., at which time the replicating virus was no longer detectable but immunological processes were still active. Consequently, the regulation of energy metabolism appears crucial for an effective virus elimination and may be of prognostic and therapeutic significance for patients with virus-induced MC.

The incidence and prevalence of systemic lupus erythematosus in Thrace, 2003-2014: A 12-year epidemiological study.

PubMed

Pamuk, O N; Balci, M A; Donmez, S; Tsokos, G C

2016-01-01

We estimated the prevalence and incidence, clinical features, treatment, and prognosis of systemic lupus erythematosus (SLE) patients in the Thrace region of Turkey. We retrospectively evaluated 331 patients (307 female, 24 male, mean age 38.5 years) diagnosed with SLE between 2003 and 2014. Clinical features, treatments, and response to various treatment modalities were recorded. Our hospital has been the only tertiary referral center for rheumatological diseases for a mixed rural and urban population of 620,477 people (306,036 females, 314,411 males) for more than 16 years. The mean annual incidence of SLE was 4.44/100,000 (females, 8.4/100,000; males, 0.6/100,000). The overall prevalence of SLE was 51.7/100,000 (females, 97.7/100,000; males, 7/100,000). Major organ involvement was present in the following percentages: neurologic involvement: 20.1%; renal involvement: 28.2%; autoimmune hemolytic anemia: 9.6%; thrombocytopenia: 14.7%. Seventeen SLE patients (13 females, four males) died at a median follow-up of 48 months. The five-year survival was 94.5%, and the ten-year survival was 89.9%. According to Kaplan-Meier survival analysis, poor prognostic factors were: male gender (p = 0.015); smoking (p = 0.02); pleural involvement (p = 0.011); thrombocytopenia (p = 0.021); myocarditis (p = 0.028); renal involvement (p = 0.037); treatment with cyclophosphamide (p = 0.011); and an initial high SLEDAI score (>4) (p = 0.02). Lymphopenia at the time of diagnosis appeared as a favorable prognostic factor (p = 0.008). Cox regression analysis revealed myocarditis (OR: 20.4, p = 0.018) and age at diagnosis (OR: 1.11, p = 0.035) to be poor, and lymphopenia at the time of diagnosis to be good prognostic factors (OR:0.13, p = 0.031). The annual incidence and prevalence of SLE in the Thrace region of Turkey is lower than those reported in North America, however they are similar to those reported for European countries. Clinical manifestations appear to be milder, whereas survival was similar to those recorded in Western countries. © The Author(s) 2015.

Coenzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem.

PubMed

Zozina, Vladlena I; Covantev, Serghei; Goroshko, Olga A; Krasnykh, Liudmila M; Kukes, Vladimir G

2018-04-15

The burden of cardiovascular and metabolic diseases is increasing with every year. Although the management of these conditions has improved greatly over the years it is still far from perfect. With all of this in mind, there is a need for new methods of prophylaxis and treatment. Coenzyme Q10 (CoQ10) is an essential compound of the human body. There is growing evidence that CoQ10 is tightly linked to cardiometabolic disorders. Its supplementation can be useful in a variety of chronic and acute disorders. This review analyses the role of CoQ10 in hypertension, ischemic heart disease, myocardial infarction, heart failure, viral myocarditis, cardiomyopathies, cardiac toxicity, dyslipidemia, obesity, type 2 diabetes mellitus, metabolic syndrome, cardiac procedures and resuscitation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

First report of Angiostrongylus vasorum in a wild red fox (Vulpes vulpes) from Apulia (Italy).

PubMed

Passantino, Giuseppe; Marino, Fabio; Gaglio, Gabriella; Patruno, Rosa; Lanteri, Giovanni; Zizzo, Nicola

2017-04-05

Severe lung strongylosis was detected in a wild red fox (Vulpes vulpes) (1/12) from Apulia (Italy). We performed routine diagnostics on 12 foxes found dead in Apulia. Eleven of them showed lesions consistent with a vehicle collision. However, the remaining fox appeared to have died from other causes. At necropsy we observed, catarrhal enteritis, fatty liver, lung congestion with some areas rm in consistence and brain haemorrhages and malacia. Histopathology revealed lung brosis with mononucleate cells in ltration, thrombosis a several larval nematodes spread in the parenchyma, interstitial nephritis, interstitial myocarditis, encephalitis, encephalomalacia, and a brain granuloma. The larvae recovered from the lung parenchyma were identi ed as the rst stage larvae of Angiostrongylus vasorum. This is the rst documented report of angiostrongylosis in a fox in Southern Italy.

Eosinophilic myocarditis due to Churg-Strauss syndrome mimicking reversible dilated cardiomyopathy.

PubMed

Chen, Ming-xian; Yu, Bi-lian; Peng, Dao-quan; Zhou, Sheng-hua

2014-01-01

A 41-year-old woman with a history of asthma arrived at the emergency room of our hospital with dyspnea. The electrocardiogram showed no specific results. Echocardiography defects revealed an obvious decrease in the left ventricular systolic function and enlargement of the left chamber. We initially considered her condition to be dilated cardiomyopathy. However, she had eosinophilia in the peripheral blood and elevated cardiac enzymes. The coronary angiography showed normal coronary arteries. Single photon emission computed tomography (SPECT) showed infiltrative myocardial disease. She was then diagnosed with eosinophil infiltrations. Combined with peripheral nerve injury and lung involvement, she was diagnosed as having Churg-Strauss syndrome. After initiating prednisone treatment, her eosinophilia and rising cardiac enzymes recovered to normal, and both her echocardiographic abnormalities and symptoms noticeably improved. Copyright © 2014 Elsevier Inc. All rights reserved.

Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment.

PubMed

Komamura, Kazuo; Fukui, Miho; Iwasaku, Toshihiro; Hirotani, Shinichi; Masuyama, Tohru

2014-07-26

In 1990, takotsubo cardiomyopathy (TCM) was first discovered and reported by a Japanese cardiovascular specialist. Since then, this heart disease has gained worldwide acceptance as an independent disease entity. TCM is an important entity that differs from acute myocardial infarction. It occurs more often in postmenopausal elderly women, is characterized by a transient hypokinesis of the left ventricular (LV) apex, and is associated with emotional or physical stress. Wall motion abnormality of the LV apex is generally transient and resolves within a few days to several weeks. Its prognosis is generally good. However, there are some reports of serious TCM complications, including hypotension, heart failure, ventricular rupture, thrombosis involving the LV apex, and torsade de pointes. It has been suggested that coronary spasm, coronary microvascular dysfunction, catecholamine toxicity and myocarditis might contribute to the pathogenesis of TCM. However, its pathophysiology is not clearly understood.

Suspected Legionella-induced perimyocarditis in an adult in the absence of pneumonia: a rare clinical entity.

PubMed

Burke, Peter T; Shah, Roshni; Thabolingam, Raveend; Saba, Souheil

2009-01-01

Legionella infection can manifest itself in many clinical forms, most commonly as pneumonia, but rarely in the form of myocardial involvement. Legionella with myocardial involvement independent of pneumonia is almost never seen in the adult population and therefore is cited only a handful of times in the medical literature. When reported, Legionella carditis itself typically occurs as an isolated pericarditis with effusion. Cases of isolated Legionella with myocardial involvement, but without associated pneumonia, have been reported among children. To our knowledge, there are no reported cases of Legionella myocarditis and pericarditis presenting concurrently with or without pneumonia, in either an adult or a pediatric population. Herein, we report a rare manifestation of Legionella pneumophila-induced perimyocarditis (strongly suspected, if not incontrovertibly proved) in an adult, in the absence of pneumonia.

Kikuchi-Fujimoto disease: an unusual association with acute renal failure.

PubMed

Silva, Amanda Feliciano da; Focaccia, Roberto; Oliveira, Allan Constantino de; Sementilli, Angelo; Reis, Gelvana Flávio Barreto

2010-01-01

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis of unknown etiopathogenesis, is a self-limited disease which frequently appears as feverish lymphadenomegaly, thus creating the need for differential diagnosis with lymphoma, systemic lupus erythematosus (SLE), infectious mononucleosis, cat-scratch disease, and toxoplasmosis with lymphonodal impairment. However, there are cases in which it may evolve with complications such as aseptic meningitis, cerebellar ataxia, and aseptic myocarditis. We are presenting a case of a 24-year-old man who had an initial picture of arthralgia, evening fever and adenomegaly. Kikuchi disease was diagnosed through lymph node biopsy with immunohistochemistry and evolves with severe systemic manifestations, such as pericarditis with cardiac tamponade, pneumonitis, hepatitis, and acute kidney failure - the latter has not been reported in literature yet. There was significant improvement of the clinical picture with prednisone.

Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

PubMed Central

Hasham, Muneer G.; Baxan, Nicoleta; Stuckey, Daniel J.; Branca, Jane; Perkins, Bryant; Dent, Oliver; Duffy, Ted; Hameed, Tolani S.; Stella, Sarah E.; Bellahcene, Mohammed; Schneider, Michael D.; Harding, Sian E.; Rosenthal, Nadia

2017-01-01

ABSTRACT Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity. PMID:28250051

Clinical and electrocardiographic presentations of transient trifascicular block in three cats.

PubMed

Oxford, Eva M; Giacomazzi, Flavia B; Moïse, N Sydney; Santilli, Roberto A

2018-06-01

This report describes transient trifascicular block in three cats presented with lethargy and inappetence, and elevated cardiac troponin I concentrations. The electrocardiogram (ECG) of cat 1 showed a sinus rhythm with pronounced first-degree atrioventricular (AV) block, right bundle branch block, and left anterior fascicular block. The ECG of cat 2 showed truncular left bundle branch block alternating with left anterior fascicular block coupled with prolonged PR intervals, second-degree heart block, and paroxysmal third-degree AV block. The ECG of cat 3 showed first-degree AV block with concomitant right bundle branch block. The diagnosis of trifascicular block was made when paroxysmal third-degree AV block was documented. All cats recovered with medical management within weeks. Each cat resumed a sinus rhythm. Elevated cardiac troponin I concentrations suggested myocarditis that improved. Copyright © 2018 Elsevier B.V. All rights reserved.

Hemophagocytic syndrome as one of the main primary manifestations in acute systemic lupus erythematosus--case report and literature review.

PubMed

Carvalheiras, G; Anjo, D; Mendonça, T; Vasconcelos, C; Farinha, F

2010-05-01

Hemophagocytic syndrome is an unusual but fatal disorder characterized by pancytopenia and activation of macrophages. We describe one case of acute systemic lupus erythematosus with an unusual presentation of hemophagocytic syndrome not related to infection. The patient presented with pancytopenia related to increasing hemophagocytic activity of histiocytes in the bone marrow. Concomitant class IV World Health Organization lupus nephritis, serositis, high titer of antinuclear factor and positive test for anti-DNA antibody fitted the diagnostic criteria of systemic lupus erythematosus. She also presented with alveolar hemorrhage and lupus myocarditis. She underwent immunosuppressive therapy with recovery from the hemophagocytic syndrome. Therefore, diagnosis of acute lupus hemophagocytic syndrome was made. The clinical presentation, laboratory diagnosis, and management of the patient are discussed and the literature was reviewed and presented, with emphasis on a possible distinct lupus subset, which includes a more aggressive systemic disease with heart involvement.

Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

PubMed

Nakamura, R K; Russell, N J; Shelton, G D

2012-06-01

A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog. © 2012 British Small Animal Veterinary Association.

Canine parvovirus infection in Australia during 1980.

PubMed

Sabine, M; Herbert, L; Love, D N

1982-06-12

A questionnaire sent to all veterinary practitioners in Australia and many in New Zealand asking for details of their experience with canine parvovirus infections in 1980 elicited the following information. In 1980 explosive outbreaks of disease occurred in most parts of Australia. There was no obvious pattern of spread over the continent as a whole. In many cases outbreaks in country areas occurred after dog shows. Canine parvovirus enteritis affected all age groups with an overall mortality of 16 per cent. While the death rate in the young was high, most dogs responded well to fluid therapy. Canine parvovirus did not appear to be associated with clinical entities other than gastroenteritis and myocarditis. No connection with reproductive problems was established. Killed canine parvovirus vaccines were used extensively after the initial release for sale in July 1980. The vaccines appeared to be safe and effective at least in the short term. Problems arose only in vaccination of very young animals.

Manifestations of Lyme carditis.

PubMed

Kostić, Tomislav; Momčilović, Stefan; Perišić, Zoran D; Apostolović, Svetlana R; Cvetković, Jovana; Jovanović, Andriana; Barać, Aleksandra; Šalinger-Martinović, Sonja; Tasić-Otašević, Suzana

2017-04-01

The first data of Lyme carditis, a relatively rare manifestation of Lyme disease, were published in eighties of the last century. Clinical manifestations include syncope, light-headedness, fainting, shortness of breath, palpitations, and/or chest pain. Atrioventricular (AV) electrical block of varying severity presents the most common conduction disorder in Lyme carditis. Although is usually mild, AV block can fluctuates rapidly and progress from a prolonged P-R interval to a His-Purkinje block within minutes to hours and days. Rarely, Lyme disease may be the cause of endocarditis, while some studies and reports, based on serological and/or molecular investigations, have suggested possible influence of Borrelia burgdorferi on degenerative cardiac valvular disease. Myocarditis, pericarditis, pancarditis, dilated cardiomyopathy, and heart failure have also been described as possible manifestations of Lyme carditis. The clinical course of Lyme carditis is generally mild, short term, and in most cases, completely reversible after adequate antibiotic treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical Features and Neurologic Complications of Children Hospitalized With Chikungunya Virus in Honduras.

PubMed

Samra, José A; Hagood, Nancy L; Summer, Andrea; Medina, Marco T; Holden, Kenton R

2017-07-01

The first case of Chikungunya virus in Honduras was identified in 2014. The virus has spread widely across Honduras via the Aedes aegypti mosquito, leading to an outbreak of Chikungunya virus (CHIKV) in 2015 that significantly impacted children. A retrospective chart review of 235 children diagnosed with CHIKV and admitted to the National Autonomous University of Honduras Hospital Escuela (Hospital Escuela) in Tegucigalpa, Honduras, was accomplished with patients who were assessed for clinical features and neurologic complications. Of 235 children admitted to Hospital Escuela with CHIKV, the majority had symptoms of fever, generalized erythematous rash, and irritability. Fourteen percent had clinical arthritis. Ten percent of patients had seizures. Six percent had meningoencephalitis. There were 2 childhood deaths during the course of this study, one from meningoencephalitis and another from myocarditis. Chikungunya virus can cause severe complications in children, the majority of which impact the central nervous system.

Structure of Ljungan virus provides insight into genome packaging of this picornavirus

NASA Astrophysics Data System (ADS)

Zhu, Ling; Wang, Xiangxi; Ren, Jingshan; Porta, Claudine; Wenham, Hannah; Ekström, Jens-Ola; Panjwani, Anusha; Knowles, Nick J.; Kotecha, Abhay; Siebert, C. Alistair; Lindberg, A. Michael; Fry, Elizabeth E.; Rao, Zihe; Tuthill, Tobias J.; Stuart, David I.

2015-10-01

Picornaviruses are responsible for a range of human and animal diseases, but how their RNA genome is packaged remains poorly understood. A particularly poorly studied group within this family are those that lack the internal coat protein, VP4. Here we report the atomic structure of one such virus, Ljungan virus, the type member of the genus Parechovirus B, which has been linked to diabetes and myocarditis in humans. The 3.78-Å resolution cryo-electron microscopy structure shows remarkable features, including an extended VP1 C terminus, forming a major protuberance on the outer surface of the virus, and a basic motif at the N terminus of VP3, binding to which orders some 12% of the viral genome. This apparently charge-driven RNA attachment suggests that this branch of the picornaviruses uses a different mechanism of genome encapsidation, perhaps explored early in the evolution of picornaviruses.

Extracellular matrix directions estimation of the heart on micro-focus x-ray CT volumes

NASA Astrophysics Data System (ADS)

Oda, Hirohisa; Oda, Masahiro; Kitasaka, Takayuki; Akita, Toshiaki; Mori, Kensaku

2017-03-01

In this paper we propose an estimation method of extracellular matrix directions of the heart. Myofiber are surrounded by the myocardial cell sheets whose directions have strong correspondence between heart failure. Estimation of the myocardial cell sheet directions is difficult since they are very thin. Therefore, we estimate the extracellular matrices which are touching to the sheets as if piled up. First, we perform a segmentation of the extracellular matrices by using the Hessian analysis. Each extracellular matrix region has sheet-like shape. We estimate the direction of each extracellular matrix region by the principal component analysis (PCA). In our experiments, mean inclination angles of two normal canine hearts were 50.6 and 46.2 degrees, while the angle of a failing canine heart was 57.4 degrees. This results well fit the anatomical knowledge that failing hearts tend to have vertical myocardical cell sheets.

Septicemic listeriosis in wild hares from Saskatchewan, Canada.

PubMed

Rothenburger, Jamie L; Bennett, Katarina R; Bryan, Lorraine; Bollinger, Trent K

2015-04-01

The bacterium Listeria monocytogenes causes disease in a wide variety of mammals including rabbits and hares. We describe naturally acquired metritis and septicemic listeriosis in wild female hares from Saskatchewan, Canada. Between April 2012 and July 2013, two white-tailed jackrabbits (Lepus townsendii) and a snowshoe hare (Lepus americanus) were presented to the Veterinary Medical Centre at the Western College of Veterinary Medicine, Saskatoon, Saskatchewan, Canada with nonspecific neurologic signs. The hares were euthanized and autopsied. Necrotizing fibrinosuppurative metritis was present in all. Additional findings in individual hares included fetal maceration, multifocal necrotizing myocarditis, multifocal hepatic necrosis, and nonsuppurative encephalitis. Listeria monocytogenes was cultured from multiple tissues in each hare. Although listeriosis in pregnant domestic rabbits has been studied, this is the first detailed description in wild North American hares. The epidemiology of listeriosis, including prevalence and the role of environmental sources and coprophagy in transmission among hares, requires further investigation.

[Segmental wall movement of the left ventricle in healthy persons and myocardial infarct patients studied by a catheter-less nuclear medical method (camera-cinematography of the heart)].

PubMed

Geffers, H; Sigel, H; Bitter, F; Kampmann, H; Stauch, M; Adam, W E

1976-08-01

Camera-Kinematography is a nearly noninvasive method to investigate regional motion of the myocard, and allows evaluation of the function of the heart. About 20 min after injection of 15-20 mCi of 99mTC-Human-Serum-Albumin, when the tracer is distributed homogenously within the bloodpool, data acquisition starts. Myocardial wall motion is represented in an appropriate quasi three-dimensional form. In this representation scars can be revealed as "silent" (akinetic) regions, aneurysms by asynchronic motion. Time activity curves for arbitrarily chosen regions can be calculated and give an equivalent for regional volume changes. 16 patients with an old infarction have been investigated. In fourteen cases the location and extent of regions with abnormal motion could be evaluated. Only two cases of a small posterior wall infarction did not show deviations from normal contraction pattern.

Improved crystallization of the coxsackievirus B3 RNA-dependent RNA polymerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jabafi, Ilham; Selisko, Barbara; Coutard, Bruno

2007-06-01

The first crystal of a coxsackievirus RNA-dependent RNA polymerase is reported. The Picornaviridae virus family contains a large number of human pathogens such as poliovirus, hepatitis A virus and rhinoviruses. Amongst the viruses belonging to the genus Enterovirus, several serotypes of coxsackievirus coexist for which neither vaccine nor therapy is available. Coxsackievirus B3 is involved in the development of acute myocarditis and dilated cardiomyopathy and is thought to be an important cause of sudden death in young adults. Here, the first crystal of a coxsackievirus RNA-dependent RNA polymerase is reported. Standard crystallization methods yielded crystals that were poorly suited tomore » X-ray diffraction studies, with one axis being completely disordered. Crystallization was improved by testing crystallization solutions from commercial screens as additives. This approach yielded crystals that diffracted to 2.1 Å resolution and that were suitable for structure determination.« less

Evaluation of an electrocardiogram on QR code.

PubMed

Nakayama, Masaharu; Shimokawa, Hiroaki

2013-01-01

An electrocardiogram (ECG) is an indispensable tool to diagnose cardiac diseases, such as ischemic heart disease, myocarditis, arrhythmia, and cardiomyopathy. Since ECG patterns vary depend on patient status, it is also used to monitor patients during treatment and comparison with ECGs with previous results is important for accurate diagnosis. However, the comparison requires connection to ECG data server in a hospital and the availability of data connection among hospitals is limited. To improve the portability and availability of ECG data regardless of server connection, we here introduce conversion of ECG data into 2D barcodes as text data and decode of the QR code for drawing ECG with Google Chart API. Fourteen cardiologists and six general physicians evaluated the system using iPhone and iPad. Overall, they were satisfied with the system in usability and accuracy of decoded ECG compared to the original ECG. This new coding system may be useful in utilizing ECG data irrespective of server connections.

Structure of Ljungan virus provides insight into genome packaging of this picornavirus.

PubMed

Zhu, Ling; Wang, Xiangxi; Ren, Jingshan; Porta, Claudine; Wenham, Hannah; Ekström, Jens-Ola; Panjwani, Anusha; Knowles, Nick J; Kotecha, Abhay; Siebert, C Alistair; Lindberg, A Michael; Fry, Elizabeth E; Rao, Zihe; Tuthill, Tobias J; Stuart, David I

2015-10-08

Picornaviruses are responsible for a range of human and animal diseases, but how their RNA genome is packaged remains poorly understood. A particularly poorly studied group within this family are those that lack the internal coat protein, VP4. Here we report the atomic structure of one such virus, Ljungan virus, the type member of the genus Parechovirus B, which has been linked to diabetes and myocarditis in humans. The 3.78-Å resolution cryo-electron microscopy structure shows remarkable features, including an extended VP1 C terminus, forming a major protuberance on the outer surface of the virus, and a basic motif at the N terminus of VP3, binding to which orders some 12% of the viral genome. This apparently charge-driven RNA attachment suggests that this branch of the picornaviruses uses a different mechanism of genome encapsidation, perhaps explored early in the evolution of picornaviruses.

Giant cell myositis responsive to combined corticosteroids and immunoglobulin.

PubMed

Shah, A; Pace, A; Hilton, D; Househam, E; Weatherby, S

2015-12-01

A 70-year-old man presented with respiratory distress and proximal muscle weakness shortly after biopsy of a left forearm mass. The biopsy showed giant cell myositis, and serological investigations identified a grossly elevated serum creatine kinase level, suggesting skeletal muscle damage. Serum troponin T was also high, but troponin I was normal. Serum antiacetylcholine receptor antibodies were positive, and imaging showed a thymoma. He recovered well following intravenous immunoglobulin and corticosteroids, and later underwent thymectomy. He is currently in sustained remission, with no clinically detectable myasthenia, but subsequently, developed hypogammaglobulinaemia. Neurologists should remember giant cell myositis/myocarditis can occur in patients who have myasthenia gravis with thymoma, as it is potentially fatal, but may respond to immunosuppression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment

PubMed Central

Komamura, Kazuo; Fukui, Miho; Iwasaku, Toshihiro; Hirotani, Shinichi; Masuyama, Tohru

2014-01-01

In 1990, takotsubo cardiomyopathy (TCM) was first discovered and reported by a Japanese cardiovascular specialist. Since then, this heart disease has gained worldwide acceptance as an independent disease entity. TCM is an important entity that differs from acute myocardial infarction. It occurs more often in postmenopausal elderly women, is characterized by a transient hypokinesis of the left ventricular (LV) apex, and is associated with emotional or physical stress. Wall motion abnormality of the LV apex is generally transient and resolves within a few days to several weeks. Its prognosis is generally good. However, there are some reports of serious TCM complications, including hypotension, heart failure, ventricular rupture, thrombosis involving the LV apex, and torsade de pointes. It has been suggested that coronary spasm, coronary microvascular dysfunction, catecholamine toxicity and myocarditis might contribute to the pathogenesis of TCM. However, its pathophysiology is not clearly understood. PMID:25068020

[Origin and evolution of canine parvovirus--a review].

PubMed

Zhao, Jianjun; Yan, Xijun; Wu, Wei

2011-07-01

Canine parvovirus (CPV-2), first recognized in 1978 as a new pathogen of dogs, was probably derived from a very closely related virus in cats, feline panleukopaenia virus (FPLV) or a closely related carnivore parvovirus (FPLV-like virus). CPV-2 is responsible for either myocarditis or fatal gastroenteritis in pups with high morbidity and mortality. Shortly after its emergence, CPV-2 has become endemic in the global dog population. The original CPV-2 continued to evolve, and was subsequently replaced by three different but closely related antigenic variants, designated CPV-2a, CPV-2b and CPV-2c, which now coexist in dog populations worldwide. The genetic and antigenic variation in CPV-2 also correlated with changes in the host range and tissue tropisms of the virus. Here, we reviewed variation and evolution of CPV-2 in past 30 years and discussed CPV-2 as an important model to study virus evolution.

Molecular characterisation and nucleotide sequence analysis of canine parvovirus strains in vaccines in India.

PubMed

Nandi, Sukdeb; Anbazhagan, Rajendra; Kumar, Manoj

2010-01-01

Canine parvovirus 2 (CPV-2) is one of the most important viruses that causes haemorrhagic gastroenteritis and myocarditis of dogs worldwide. The picture has been complicated further due to the emergence of new mutants of CPV, namely: CPV-2a, CPV-2b and CPV-2c. In this study, the molecular characterisation of strains present in the CPV vaccines available on the Indian market was performed using polymerase chain reaction and DNA sequencing. The VP1/VP2 genes of two vaccine strains and a field strain (Bhopal) were sequenced and the nucleotide and the deduced amino acid sequences were compared. The results indicated that the isolate belonged to CPV type 2b and the strains in the vaccines belonged to type CPV-2. From the study, it is inferred that the CPV strain used in commercially available vaccine preparation differed from the strains present in CPV infection in dogs in India.

Chlamydophila pneumoniae myopericarditis in a child.

PubMed

Suesaowalak, Monnipa; Cheung, Michele M; Tucker, Dawn; Chang, Anthony C; Chu, James; Arrieta, Antonio

2009-04-01

An 11-year-old boy with serologically confirmed Chlamydophila pneumoniae infection presented with clinical, laboratory, and echocardiographic changes consistent with myopericarditis. No reports on C. pneumoniae myopericarditis in children are found in the medical literature. The boy, previously healthy, presented with fever, rash, constitutional symptoms, elevated acute phase reactants, elevated cardiac enzymes, and high brain natriuretic peptide levels. Hemodynamic instabilities, including hypotension and mild hypoxia, were noted. Two-dimensional echocardiographic findings showed mildly depressed left ventricular systolic function and small pericardial effusion. Requiring inotropic support, the boy was treated with azithromycin 10 mg/kg once daily for 7 days and a single dose of intravenous immunoglobulin 2 g/kg. He recovered fully with improved left ventricular systolic function before hospital discharge. An early definitive diagnosis is essential to knowing the etiology of pediatric myocarditis. Specific therapy may play role in the management and prognosis of this disorder.

Diagnostic implications of magnetic resonance feature tracking derived myocardial strain parameters in acute myocarditis.

PubMed

Baeßler, Bettina; Schaarschmidt, Frank; Dick, Anastasia; Michels, Guido; Maintz, David; Bunck, Alexander C

2016-01-01

The present study aims to evaluate the diagnostic value of cardiac magnetic resonance (CMR) feature tracking (FT) derived strain-analysis of both ventricles in patients with acute myocarditis (ACM) in order to improve its currently still challenging non-invasive diagnosis. CMR cine data of 31 patients with clinically suspected ACM and confirmation of diagnosis by CMR according to the Lake Louise criteria as well as 14 patients with clinically diagnosed ACM but inconspicuous CMR were retrospectively analyzed. 20 healthy volunteers (HV) served as a control. Analysis of global longitudinal, circumferential and radial strain and strain rate of both ventricles was performed in one long-axis and three short-axis slices using a dedicated FT-software (TomTec Imaging Systems). Patients with ACM showed significantly reduced LV longitudinal strain (-12.7 ± 6.5 vs. -16.8 ± 5.9%, p=0.021) and LV circumferential strain (LVCirStrain; -22.9 ± 5.7 vs. -27.8 ± 4.4 %, p<0.001) compared to HV. Conversely, they showed improved basal RV circumferential strain rate (BasalRVCirSR; -0.70 ± 0.23 vs. -0.47 ± 0.31s(-1), p=0.009). In ACM patients with preserved EF, BasalRVCirSR was significantly increased compared to HV while LV strain was not significantly different between both groups. In multinominal logistic regression analysis, LVCirStrain and BasalRVCirSR proved to be the best independent predictors of ACM with preserved EF. A combined cut-off of -0.53s(-1) for BasalRVCirSR and of -29.0% for LVCirStrain allowed a classification of ACM patients with preserved EF with a sensitivity of 89% and a specificity of 80%. Also patients with clinical ACM but inconspicuous CMR showed a significantly improved BasalRVCirSR and a cut-off of -0.77s(-1) allowed a classification of ACM patients with a sensitivity of 70% and a specificity of 90%, while all other CMR parameters were normal. The defined cut-offs for LVCirStrain and BasalRVCirSR allow a prediction of ACM with high sensitivity and specificity, even in patients with preserved EF and in patients with otherwise completely inconspicuous CMR. Our results point to a discriminative power especially of RV strain analysis in the CMR-based diagnosis of ACM. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The value of endomyocardial biopsy in diagnosis and guiding therapy.

PubMed

Khan, Tayyaba; Selvakumar, Dinesh; Trivedi, Siddharth; Rao, Karan; Harapoz, Mehmet; Thiagalingam, Aravinda; Denniss, A Robert; Varikatt, Winny

2017-12-01

Endomyocardial biopsy (EMB) is a highly-specialised procedure that is associated with some controversy as to its diagnostic role due to its inconsistency in diagnosing a wide variety of cardiac diseases. Given the advances and sophistication in echocardiography and cardiac magnetic resonance imaging (MRI), the vast majority of cardiac diseases can be diagnosed by these non-invasive procedures. Under-sampling and the fact that biopsy site is limited to the right side of the interventricular septum further limits its value. In spite of all these limitations, there still remains a group of pathological conditions that require biopsy for a conclusive diagnosis such as myocarditis, amyloidosis, sarcoidosis and giant cell myocarditis. Correct patient selection and the quantity of tissue samples impart a significant influence on the accuracy of the diagnosis, and thus the value of EMB is variable for each patient. The purpose of this study was to evaluate the role of EMB in patient care, through its ability to either change clinical diagnosis or alter patient management. Our study was based in a single teaching centre. An audit of cardiac biopsies performed over a 10 year period identified 250 patients. We assessed indications, histology, electron microscopic findings, final clinical diagnosis and how they influenced patient management. A definite diagnosis on histology was given in 44 of 250 patients (17.6%). Non-specific findings were observed in the remaining 206 patients (82.4%). Histology influenced patient management in 73 (29.2%) patients. Histological examination in the remaining 177 biopsies (70.8%) did not provide a definite diagnosis or influence patient management. It was additionally found that the number of tissue fragments sampled has significant impact on diagnostic accuracy. A more accurate diagnosis of 45% was obtained when ≥5 fragments were sampled, as compared to 1-3 fragments where accuracy dropped to 20%. Our study indicated that sampling for electron microscopy has very limited value. We found that of 245 biopsies sampled for electron microscopy, only three biopsies (1.2%) had diagnostically useful findings. In our institution procedure related complications were observed in 7 of 250 patients (2.8%). The diagnostic value of EMB is important but limited. Strict triaging of patients according to clinical suspicion and adequate sampling of tissue may increase useful diagnostic information. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis: The Multicenter Lombardy Registry.

PubMed

Ammirati, Enrico; Cipriani, Manlio; Moro, Claudio; Raineri, Claudia; Pini, Daniela; Sormani, Paola; Mantovani, Riccardo; Varrenti, Marisa; Pedrotti, Patrizia; Conca, Cristina; Mafrici, Antonio; Grosu, Aurelia; Briguglia, Daniele; Guglielmetto, Silvia; Battista Perego, Giovanni; Colombo, Stefania; Caico, Salvatore Ivan; Giannattasio, Cristina; Maestroni, Alberto; Carubelli, Valentina; Metra, Marco; Lombardi, Carlo; Campodonico, Jeness; Agostoni, Piergiuseppe; Peretto, Giovanni; Scelsi, Laura; Turco, Annalisa; Di Tano, Giuseppe; Campana, Carlo; Belloni, Armando; Morandi, Fabrizio; Mortara, Andrea; Cirò, Antonio; Senni, Michele; Gavazzi, Antonello; Frigerio, Maria; Oliva, Fabrizio; Camici, Paolo G

2018-05-15

Background -There is controversy regarding outcome of patients with acute myocarditis (AM), and lack of data on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management and long-term outcome of patients with AM based on a retrospective multi-center registry from 19 Italian hospitals. Methods -A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years and those older than 50 years without coronary angiography were excluded. The final study population comprised 443 patients (median age 34 years, 19.4% female) with AM diagnosed either by endomyocardial biopsy (EMB) or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance (CMR). Results -At presentation, 118 patients (26.6%) had either left ventricular (LV) ejection fraction (EF) <50%, sustained ventricular arrhythmias (VA) or a low cardiac output syndrome (LCOS) whilst 325 (73.4%) had no such complications. EMB was performed in 56/443 (12.6%), and a baseline CMR was performed in 415/443 (93.7%) of patients. Cardiac mortality plus heart transplant (HTx) at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus HTx were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (Log-rank p<0.0001). Major AM-related cardiac events after the acute phase (post-discharge death and HTx, sustained VA treated with electrical shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at 5-year follow up, with a higher incidence in patients with complicated forms (10.8% vs. 0% in uncomplicated AM, Log-rank p<0.0001). Beta adrenoceptor blockers were the most frequently employed medications both in complicated (61.9%) and in uncomplicated forms (53.8%, p=0.18). After a median time of 196 days, 200 patients had follow-up CMR and 8/55 (14.5%) with complications at presentation had LVEF<50% compared with 1/145 (0.7%) of those with uncomplicated presentation. Conclusions -In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with LVEF<50%, VA or LCOS at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent LV systolic dysfunction.

Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Yuan-Horng; Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan; Charles, Chou C.-K.

Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM{sub 2.5} exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), tomore » continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM{sub 2.5} in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m{sup 3}, respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic homeostasis, was elevated in DM rats exposed to PM. • Inflammatory markers, IL-6 and fibrinogen, were increased in DM rats exposed to PM. • PM caused myocarditis, aortic medial thickness, and kidney damages in DM rats.« less

Endocarditis due to Lactobacillus jensenii in a Salvin's Amazon parrot (Amazona autumnalis salvini).

PubMed

Foldenauer, Ulrike; Rusch, Martina; Simova-Curd, Stefka; Nitzl, Dagmar; Hoop, Richard K; Hatt, Jean-Michel

2009-02-01

A 30-year-old Salvin's Amazon parrot (Amazona autumnalis salvini) with a history of a lifelong poor diet and inappropriate housing was presented in lateral recumbency to a veterinary teaching hospital for further evaluation. Radiological and ultrasonographic examination revealed a mild proventricular dilatation, mild hepatomegaly, signs of enteritis and airsacculitis. The main laboratory findings included a mild macrocytic hyperchromic anaemia, hypoglobulinaemia, decreased bile acids and increased alkaline phosphatase. In this bird a liver pathology was suspected because of the clinical, laboratory and ultrasonographic findings. The bird was treated with supportive care and metabolic aids. After initial improvement of the clinical signs, the bird's condition deteriorated and it died. Pathological findings revealed an endocarditis and myocarditis due to Lactobacillus jensenii and a bacteraemia. Endocarditis due to Lactobacillus sp. is a rare phenomenon in humans not yet described in animals. It is associated with severe underlying illnesses leading to translocation of otherwise non-pathogenic bacteria in the bloodstream. A similar pattern might be assumed in animals with compromised immunity.

An Unexpected Cause of Bradycardia in a Patient with Bacterial Meningitis.

PubMed

Ioannou, Petros; Velegraki, Magdalini; Soundoulounaki, Stella; Gikas, Achilleas; Kofteridis, Diamantis P

2017-01-01

Sinus bradycardia which is a sinus rhythm with a resting heart rate of less than 60 bpm is caused by intrinsic cardiac disorders like sick sinus syndrome or inferior myocardial infarction, metabolic and environmental causes (such as hypothyroidism and electrolyte disorders), medications (such as beta-blockers and amiodarone), infection (such as myocarditis), increased intracranial pressure, and toxic exposure, while it can sometimes be a normal phenomenon, especially during sleep, in athletes, and during pregnancy. Symptomatic sinus bradycardia should warrant a thorough work-up in order to identify any reversible causes; otherwise, placement of a permanent pacemaker could be needed. We present the case of a patient who was admitted due to confusion and fever and was found to have pneumococcal meningitis and bacteremia, and during his hospital stay he developed symptomatic sinus bradycardia that was of intractable cause and persistent. Placement of a permanent pacemaker was chosen until the night staff of the hospital discovered by chance the neglected cause of his bradycardia.

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

PubMed Central

GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

2017-01-01

Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity - A Case Report.

PubMed

Gerasimou, Charilaos; Vitali, Georgia Phaedra; Vavougios, George D; Papageorgiou, Charalabos; Douzenis, Athanasios; Kokoris, Styliani I; Liappas, Ioannis; Rizos, Emmanouil

2017-01-02

Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. We present the case of a 31-year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[Morphologic festures of cardiac lesions in rheumatoid arthritis].

PubMed

Kop'eva, T N

1976-11-01

Morphological examinations of the heart in cases of articulo-visceral rheumatoid arthritis revealed in 20 of the 35 conducted observations certain changes attributable to the underlying disease. The following groups of changes were revealed: 1) endocarditis; 2) myocarditis; 3) pericarditis; 4) rheumatoid nodules; 5) valvular sclerosis and mural endocarditis; 6) cardiosclerosis; 7) amyloidosis; 8) coronaritis and coronary sclerosis; 9) adhesions in the pericardial cavity. The severity of cardiac leasion in rheumatoid arthritis is determined by the involvement of the serosa into the pathological process. Inflammatory and sclerotic changes in the myocardium are predimonantly of a subepicardial and subendocardial nature, usually non-accompanied by any clear clinical symptoms, or taking a latent course. Rheumatoid nodules typical of rheumatoid arthritis, and deposits of amyloid masses in the walls of the coronary arteries are noted rarely. Changes in the heart are observed mostly in "septic", subacute rheumatoid arthritis and in Still's disease. Cardiac lesions in rheumatoid arthritis are connected with microcirculatory disorders caused by immunopathological processes.

[Bartonella henselae, an ubiquitous agent of proteiform zoonotic disease].

PubMed

Edouard, S; Raoult, D

2010-06-01

Bartonella henselae is the causative agent of cat scratch disease, a human infection usually characterized by persistent regional lymphadenopathy. It is transmitted to humans by cat scratches or bites. Cats are the major reservoir for this bacterium thus B. henselae has a worldwide distribution. The bacterial pathogenicity may bay emphasized by the immune status of the infected host. Angiomatosis or hepatic peliosis are the most frequent clinical manifestations in immunocompromised patients. B. henselae is also responsible for endocarditis in patients with valvular diseases, and may induce various clinical presentations such as: bacteriemia, retinitis, musculoskeletal disorders, hepatic or splenic diseases, encephalitis, or myocarditis. Several diagnostic tools are available; they may be combined and adapted to every clinical setting. B. henselae is a fastidious bacterium; its diagnosis is mainly made by PCR and blood tests. No treatment is required for the benign form of cat scratch disease. For more severe clinical presentations, the treatment must be adapted to every clinical presentation.

Typing of Canine Parvovirus Strains Circulating in North-East China.

PubMed

Zhao, H; Wang, J; Jiang, Y; Cheng, Y; Lin, P; Zhu, H; Han, G; Yi, L; Zhang, S; Guo, L; Cheng, S

2017-04-01

Canine parvovirus (CPV) is highly contagious and is a major cause of haemorrhagic enteritis and myocarditis in dogs. We investigated the genetic variation of emerging CPV strains by sequencing 64 CPV VP2 genes from 216 clinical samples of dogs from Heilongjiang, Jilin, Liaoning, Shandong and Hebei in 2014. Genetic analysis revealed that CPV-2b was predominant in Hebei and CPV-2a was predominant in the other four provinces. In addition, a CPV-2c strain has emerged in Shandong province. All samples had a Ser-Ala substitution at residue 297 and an Ile-Arg substitution at residue 324. Interestingly, in five separate canine samples, we found a mutation of Gln370 to Arg, until now detected only in isolates from pandas. The phylogenetic analysis showed clear distinctions between epidemic isolates and vaccine strains and between Chinese CPV-2c strains and CPV-2c strains found in other countries. Monitoring recent incidence of CPV strains enables evaluation and implementation of disease control strategies. © 2015 Blackwell Verlag GmbH.

Full-length genomic characterization and molecular evolution of canine parvovirus in China.

PubMed

Zhou, Ling; Tang, Qinghai; Shi, Lijun; Kong, Miaomiao; Liang, Lin; Mao, Qianqian; Bu, Bin; Yao, Lunguang; Zhao, Kai; Cui, Shangjin; Leal, Élcio

2016-06-01

Canine parvovirus type 2 (CPV-2) can cause acute haemorrhagic enteritis in dogs and myocarditis in puppies. This disease has become one of the most serious infectious diseases of dogs. During 2014 in China, there were many cases of acute infectious diarrhoea in dogs. Some faecal samples were negative for the CPV-2 antigen based on a colloidal gold test strip but were positive based on PCR, and a viral strain was isolated from one such sample. The cytopathic effect on susceptible cells and the results of the immunoperoxidase monolayer assay, PCR, and sequencing indicated that the pathogen was CPV-2. The strain was named CPV-NY-14, and the full-length genome was sequenced and analysed. A maximum likelihood tree was constructed using the full-length genome and all available CPV-2 genomes. New strains have replaced the original strain in Taiwan and Italy, although the CPV-2a strain is still predominant there. However, CPV-2a still causes many cases of acute infectious diarrhoea in dogs in China.

[Acute coronary syndrome as a first manifestation of Churg-Strauss syndrome].

PubMed

Asdonk, T; Pabst, S; Clauberg, R; Schaefer, C; Skowasch, D; Nickenig, G; Tiyerili, V

2012-03-01

A 53-year-old woman was admitted to our chest pain unit because of an acute coronary syndrome (non ST-elevation myocardial infarction). She complained of asthma, chronic sinusitis and involuntary weight loss, occasional fever and night sweats over the past six months. Coronary angiography did not show any signs of macroscopic coronary artery disease, while echocardiography demonstrated a hemodynamically not significant pericardial effusion. Magnetic resonance imaging of the heart revealed a subendocardial scar, extension and localization pointing to a vascular genesis. Thoracic computed tomography revealed pulmonary opacities and blood tests showed an eosinophilia, leading to the clinical diagnosis of Churg-Strauss syndome. The patient responded quickly to oral steroids, and blood parameters returned to normal. Acute coronary syndrome in youngish patients without classical cardiovascular risk factors is suggestive for myocarditis but also for vasculitis. Churg-Strauss syndrome usually responds quickly to immunosuppressive therapy, associated with a rather good prognosis without high mortality. © Georg Thieme Verlag KG Stuttgart · New York.

Multimodality Imaging in Cardiooncology

PubMed Central

Pizzino, Fausto; Vizzari, Giampiero; Qamar, Rubina; Bomzer, Charles; Carerj, Scipione; Khandheria, Bijoy K.

2015-01-01

Cardiotoxicity represents a rising problem influencing prognosis and quality of life of chemotherapy-treated patients. Anthracyclines and trastuzumab are the drugs most commonly associated with development of a cardiotoxic effect. Heart failure, myocardial ischemia, hypertension, myocarditis, and thrombosis are typical manifestation of cardiotoxicity by chemotherapeutic agents. Diagnosis and monitoring of cardiac side-effects of cancer treatment is of paramount importance. Echocardiography and nuclear medicine methods are widely used in clinical practice and left ventricular ejection fraction is the most important parameter to asses myocardial damage secondary to chemotherapy. However, left ventricular ejection decrease is a delayed phenomenon, occurring after a long stage of silent myocardial damage that classic imaging methods are not able to detect. New imaging techniques including three-dimensional echocardiography, speckle tracking echocardiography, and cardiac magnetic resonance have demonstrated high sensitivity in detecting the earliest alteration of left ventricular function associated with future development of chemotherapy-induced cardiomyopathy. Early diagnosis of cardiac involvement in cancer patients can allow for timely and adequate treatment management and the introduction of cardioprotective strategies. PMID:26300915

Aleutian Disease: An Emerging Disease in Free-Ranging Striped Skunks (Mephitis mephitis) From California.

PubMed

LaDouceur, E E B; Anderson, M; Ritchie, B W; Ciembor, P; Rimoldi, G; Piazza, M; Pesti, D; Clifford, D L; Giannitti, F

2015-11-01

Aleutian disease virus (ADV, Amdovirus, Parvoviridae) primarily infects farmed mustelids (mink and ferrets) but also other fur-bearing animals and humans. Three Aleutian disease (AD) cases have been described in captive striped skunks; however, little is known about the relevance of AD in free-ranging carnivores. This work describes the pathological findings and temporospatial distribution in 7 cases of AD in free-ranging striped skunks. All cases showed neurologic disease and were found in a 46-month period (2010-2013) within a localized geographical region in California. Lesions included multisystemic plasmacytic and lymphocytic inflammation (ie, interstitial nephritis, myocarditis, hepatitis, meningoencephalitis, pneumonia, and splenitis), glomerulonephritis, arteritis with or without fibrinoid necrosis in several organs (ie, kidney, heart, brain, and spleen), splenomegaly, ascites/hydrothorax, and/or encephalomalacia with cerebral microangiopathy. ADV infection was confirmed in all cases by specific polymerase chain reaction and/or in situ hybridization. The results suggest that AD is an emerging disease in free-ranging striped skunks in California. © The Author(s) 2014.

Eosinophils in Autoimmune Diseases

PubMed Central

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

Right Ventricular Myocardial Ischemia with Arrhythmia in an Asphyxiated Newborn

PubMed Central

Solevåg, Anne Lee; Schmölzer, Georg M.; Cheung, Po-Yin

2016-01-01

Background Infant and neonatal myocardial infarction (MI) has been described in association with congenital heart disease, coronary artery abnormalities, myocarditis, and tumors. MI in the perinatal period in a structurally normal heart and with ventricular arrhythmia as a presenting feature has not been thoroughly described. Published case reports describe treatment methods extrapolated from adult MI. However, due to the rare occurrence, the most appropriate acute treatment for both MI and ventricular arrhythmia in newborn infants remains unknown. Case A male term infant with perinatal asphyxia and need for extensive cardiopulmonary resuscitation at birth had ventricular tachyarrhythmia and ST-elevations on electrocardiogram. Four hours after birth, he died from cardiogenic failure. A thrombus at the right coronary artery was found on autopsy. Conclusion MI in the perinatal period in a structurally normal heart is very rare and mortality is high. Although acute treatments extrapolated from adult MI has been described to result in favorable outcomes in newborn infants, guidelines are lacking on how to manage acute MI and associated ventricular arrhythmia. PMID:27280062

Sudden death in sports among young adults in Norway.

PubMed

Solberg, Erik Ekker; Gjertsen, Finn; Haugstad, Erlend; Kolsrud, Lars

2010-06-01

The aim of the study was to explore sudden cardiac death during physical activity in young adults in Norway. This retrospective study examined adults aged 15-34 years during the period 1990-1997. The Cause of Death Registry was used to identify cases of sudden cardiac death in sports. These cases were validated with information from medical records and autopsy reports. Twenty-three sports-related sudden deaths (22 men), mean age 27 years (17-34 years), were identified. Causes of death were myocardial infarction (11), myocarditis (5), conduction abnormalities (2), aortic stenosis (1), cardiac rupture (1), hypertrophic obstructive cardiomyopathy (1), congenital coronary anomaly (1), and coronary sclerosis without defined infarction (1). The deaths were distributed across different types of sports activities. The incidence of deaths among physically active young men was 0.9 per 100,000. The number of myocardial infarctions is higher than expected. The incidence is similar to that found in other studies. A vast majority of the cases of death were men.

Paediatric Virology: A rapidly increasing educational challenge

PubMed Central

Mammas, Ioannis N.; Theodoridou, Maria; Kramvis, Anna; Thiagarajan, Prakash; Gardner, Sharryn; Papaioannou, Georgia; Melidou, Angeliki; Koutsaki, Maria; Kostagianni, Georgia; Achtsidis, Vassilis; Koutsaftiki, Chryssie; Calachanis, Marcos; Zaravinos, Apostolos; Greenough, Anne; Spandidos, Demetrios A.

2017-01-01

The ‘2nd Workshop on Paediatric Virology’, which took place on Saturday the 8th of October 2016 in Athens, Greece, provided an overview on recent views and advances on Paediatric Virology. Emphasis was given to HIV-1 management in Greece, a country under continuous financial crisis, hepatitis B vaccination in Africa, treatment options for hepatitis C virus in childhood, Zika virus in pregnancy and infancy, the burden of influenza on childhood, hand-foot-mouth disease and myocarditis associated with Coxsackie viruses. Other general topics covered included a critical evaluation of Paediatric Accident and Emergency viral infections, multimodality imaging of viral infections in children, surgical approaches of otolaryngologists to complex viral infections, new advances in the diagnosis and treatment of viral conjunctivitis and novel molecular diagnostic methods for HPV in childhood. A brief historical overview of the anti-vaccination movement was also provided, as well as presentations on the educational challenge of Paediatric Virology as a new subspecialty of Paediatrics. This review highlights selected lectures and discussions of the workshop. PMID:28352303

A Patient with Erythema Nodosus Leprosum and Chagas Cardiopathy: Challenges in Patient Management and Review of the Literature

PubMed Central

Trindade, Maria Ângela B.; Carvalho, Noemia B.; Belfort, Elaini C.; Pagliari, Carla; Gakiya, Erika; Sakai-Valente, Neusa Y.; Benard, Gil; Shikanai-Yasuda, Maria A.

2011-01-01

We report a patient with severe multi-bacillary leprosy complicated by recurrent episodes of erythema nodosum necrotisans that required thalidomide and/or corticosteroids during follow-up. Although the patient was from an area to which Chagas disease is endemic, this diagnosis was initially missed and was only investigated when heart failure developed in the patient. The difficulties of managing erythema nodosum necrotisans and heart failure concomitantly and those involved in excluding the diagnosis of acute myocarditis caused by reactivation of Chagas disease secondary to the immunosuppressive regimen are discussed. Other potential causes for the heart failure and possible interactions between the two diseases and their treatments are discussed. We also reviewed the literature for the association between leprosy and Chagas disease, both of which are highly endemic in Brazil. This case emphasizes the importance of searching for subclinical co-infections in leprosy patients because reactions frequently develop during specific treatment in these patients, and these reactions require prolonged therapy with immunosuppressive drugs. PMID:21633036

Autoimmune Granulomatous Inflammation of Lacrimal Glands and Axonal Neuritis Following Treatment With Ipilimumab and Radiation Therapy.

PubMed

Ileana Dumbrava, Ecaterina; Smith, Veronica; Alfattal, Rasha; El-Naggar, Adel K; Penas-Prado, Marta; Tsimberidou, Apostolia M

2018-05-21

Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response. The use of immune checkpoint inhibitors exhibit an unique toxicity profile, the immune-related adverse events (irAEs). The most notable immune reactions are noted in skin (rash), gastrointestinal track (colitis, hepatitis, pancreatitis), lung (pneumonitis), heart (myocarditis), and endocrine system (thyroiditis, hypophysitis). We present a patient with metastatic adenoid cystic carcinoma of the left submandibular gland with granulomatous inflammation of the lacrimal glands and axonal neuritis of the cervical and paraspinal nerves following treatment with ipilimumab and radiation therapy.

Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation.

PubMed

Marijanovich, Nicole; Halalau, Alexandra

2018-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation.

The Clinical Profile of Kawasaki Disease in Algerian Children: A Single Institution Experience.

PubMed

Boudiaf, Houda; Achir, Moussa

2016-04-01

Kawasaki disease (KD) in an acute vasculitis of unknown etiology. The epidemiological data available for Algerian patients remains insufficient. To describe the demographic, clinical features of children with KD and to identify the risk factors for developing coronary artery lesions (CAL). This retrospective study included children admitted with KD at the pediatric hospital in Algiers from January 2005 to December 2014. One hundred thirty-three patients (82 boys and 51 girls) with a mean age of 31 months were identified. The most common sign was fever, rash, oral changes and conjunctivitis. The cardiac complications were CAL (22.5%), pericarditis (2%) and myocarditis (1.5%). The independent variable for prediction of CAL was duration of fever >10 days, male gender and platelet count >450,000/mm3 CONCLUSION: The incidence of cardiovascular complications is high. Knowledge of KD among Algerian pediatricians should be enhanced to guarantee appropriate treatment of this disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation

PubMed Central

Marijanovich, Nicole

2018-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation. PMID:29610699

Disseminated mycosis in a killer whale (Orcinus orca).

PubMed

Abdo, Walied; Kawachi, Takeshi; Sakai, Hiroki; Fukushi, Hideto; Kano, Rui; Shibahara, Tomoyuki; Shirouzu, Hiroshi; Kakizoe, Yuko; Tuji, Hajime; Yanai, Tokuma

2012-01-01

Hematological findings in a female killer whale (Orcinus orca) undergoing rehabilitation after sudden severe anorexia revealed continuing increases in serum lactate dehydrogenase and aspartate aminotransferase activities as well as fibrinogen concentration. Serologic evidence of herpesvirus infection and skin vesicles were detected 2 weeks into the treatment regimen of antibiotics and corticosteroids. The whale showed signs of improvement after treatment with anti-herpesvirus drugs, but sudden severe anorexia reappeared, along with marked elevation of fibrinogen concentration that continued until the death. Postmortem examination revealed multiple light tan foci of necrosis in the skeletal and cardiac muscles, and lung consolidation. Microscopic findings indicated disseminated fungal granulomas in the skeletal and cardiac muscles, as well as myocarditis, mycotic embolic thromboarteritis of cardiac blood vessels, and bronchopneumonia with numerous typical Aspergillus-like fungi. Mucor-like structures in granulomas in the heart and skeletal muscle and Aspergillus-like fungi in the lungs were identified using periodic acid-Schiff, Gomori methenamine silver stain, and immunohistochemistry. The present case involves dual infection with Mucor and Aspergillus species in a killer whale with concurrent herpesvirus.

Rabies among African wild dogs (Lycaon pictus) in the Masai Mara, Kenya.

PubMed

Kat, P W; Alexander, K A; Smith, J S; Richardson, J D; Munson, L

1996-10-01

A pack of African wild dogs (Lycaon pictus) ranging to the north of the Masai Mara National Reserve in southwestern Kenya was monitored from 1988 to 1989. During a 6-week period (August 1-September 13, 1989), 21 of 23 members of this pack died. Seven carcasses were retrieved, of which 4 were suitable for necropsy and histopathologic examination. Gross findings varied among individuals and included multiple bite wounds, synovitis, lymphadenopathy, submandibular, cervical, and vocal cord edema, blood in bronchi, bronchioles, stomach, and intestine, and interioventral lung lobe consolidation. Histologic examination of 2 available brain samples revealed nonsuppurative encephalitis with eosinophilic intracytoplasmic inclusions (Negri bodies). An additional brain sample tested positive for rabies via a fluorescent antibody test. Other histologic features included severe suppurative bronchopneumonia, myocarditis, and lymphoid depletion of the lymph nodes, tonsils, and spleen. A 304-base pair (bp) nucleotide sequence from the N gene and a 310-bp sequence from the G gene from rabies isolates of 4 wild dogs indicated that infection was with a rabies variant common among domestic dogs in Kenya and Tanzania.

Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy.

PubMed Central

Andrade, Z. A.; Andrade, S. G.; Correa, R.; Sadigursky, M.; Ferrans, V. J.

1994-01-01

Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:8203476

Kawasaki disease: a rare pediatric pathology in Mexico. Twenty cases report from the Hospital Infantil del Estado de Sonora.

PubMed

Sotelo, Norberto; González, Luis Antonio

2007-01-01

Kawasaki disease (KD) is an etiological illness that is relatively unknown and scarcely identified in Mexico; it affects children mainly aged 1-4 years, evolves with fever, vasculitis in diverse organs, and in the heart the disease mainly affects the coronary arteries. Our aim was to inform the clinical findings and evolution of 20 patients diagnosed with KD. We reviewed the patient clinical files retrospectively and descriptively to obtain information with regard to age, sex, clinical signs, laboratory and consultory results, echocardiography findings, complications, evolution during hospitalization, followup, and out-patient ambulatory consultations. Eighteen patients were male, two were female, six developed coronary damage, two aortic mitral-valve insufficiency, one pericardial shedding, and one, myocarditis. All patients received gamma globulin treatment with aspirin, and 16 were controlled during 6-8 months after the acute medical profile. The opportune clinical diagnostic it is fundamental to establish an early treatment with gammmaglobuline to avoid injuries in the arterial coronary level. This injury may cause eventualy ischemia or myocardial infarct

Single-incision video-assisted thoracoscopic evaluation and emergent surgery for severe lung and chest wall injury after thoracic trauma in a water park.

PubMed

Sesma, Julio; Alvarez, Melodie; Lirio, Francisco; Galvez, Carlos; Galiana, Maria; Baschwitz, Benno; Fornes, Francisca; Bolufer, Sergio

2017-08-01

Thoracic trauma is a challenging situation with potential severe chest wall and intrathoracic organ injuries. We present a case of emergent surgery in a 23-year-old man with hemorrhagic shock due to massive lung and chest wall injury after thoracic trauma in a water slide. We performed a SI-VATS approach in order to define intrathoracic and chest wall injuries, and once checked the extension of the chest wall injury, we added a middle size thoracotomy just over the affected area in order to stabilize rib fractures with Judet plates, that had caused massive laceration in left lower lobe (LLL) and injured the pericardium causing myocardical tear. After checking bronchial and vascular viability of LLL we suggested a lung parenchyma preserving technique with PTFE protected pulmonary primary suture in order to avoid a lobectomy. Chest tubes were removed on 3 rd postoperative day and patient was discharged on 14 th postoperative day. He has already recovered his normal activity 6 months after surgery.

Single-incision video-assisted thoracoscopic evaluation and emergent surgery for severe lung and chest wall injury after thoracic trauma in a water park

PubMed Central

Alvarez, Melodie; Lirio, Francisco; Galvez, Carlos; Galiana, Maria; Baschwitz, Benno; Fornes, Francisca; Bolufer, Sergio

2017-01-01

Thoracic trauma is a challenging situation with potential severe chest wall and intrathoracic organ injuries. We present a case of emergent surgery in a 23-year-old man with hemorrhagic shock due to massive lung and chest wall injury after thoracic trauma in a water slide. We performed a SI-VATS approach in order to define intrathoracic and chest wall injuries, and once checked the extension of the chest wall injury, we added a middle size thoracotomy just over the affected area in order to stabilize rib fractures with Judet plates, that had caused massive laceration in left lower lobe (LLL) and injured the pericardium causing myocardical tear. After checking bronchial and vascular viability of LLL we suggested a lung parenchyma preserving technique with PTFE protected pulmonary primary suture in order to avoid a lobectomy. Chest tubes were removed on 3rd postoperative day and patient was discharged on 14th postoperative day. He has already recovered his normal activity 6 months after surgery. PMID:28861425

[Pheochromocytoma and cardiogenic failure: an indication for emergency adrenalectomy].

PubMed

Vandwalle, J; Spie, R; Jarry, G; Agaesse, V; Petit, J; Saint, F

2010-07-01

To identify cardiogenic failure or cardiogenic shock associated with pheochromocytoma diagnosis and emergency adrenalectomy. Update this unusual presentation of pheochromocytoma. Between 1998 and 2009, 119 adrenalectomies were performed in our department, among which 19 cases for pheochromocytoma. We reported three cases with cardiogenic failure or cardiogenic shock associated with emergency adrenalectomy. Patients were 36, 41 and 67 years old. The elapsed time between cardiogenic failure and surgery was 0, 7 and 19 days. The first diagnosis was a viral myocarditis in those three cases. The diagnosis of adrenal pheochromocytoma was done in a second step by the association of adrenal tumour on abdominal CT scan and detection of significantly elevated plasma/urine catecholamine. Severe systolic dysfunction with low ejection fraction was associated in all cases. Cardiac function was quickly restored after adrenalectomy. Cardiac emergency associated with pheochromocytoma is an unusual clinical presentation. When diagnosis fails to be performed, patients have a very poor prognosis. According to a review of the sparse literature, only early recognition and emergency adrenalectomy can improve the outcome. Copyright 2010. Published by Elsevier Masson SAS.

New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma.

PubMed

Behling, Juliane; Kaes, Joachim; Münzel, Thomas; Grabbe, Stephan; Loquai, Carmen

2017-04-01

There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivolumab, our patient developed a troponin I-positive and autoantibody-positive myositis and a few days later a new-onset third-degree atrioventricular block. This is most likely because of an autoimmune-induced myositis with a cardiac impairment in terms of a myocarditis, which led to an impairment of the conduction of cardiac electrical stimuli.

Neospora caninum abortion in a Malayan tapir (Tapirus indicus).

PubMed

Peters, M; Osmann, C; Wohlsein, P; Schares, G

2017-05-30

A captive 17-year old female Malayan tapir (Tapirus indicus) aborted a fetus with a crown rump length of 19cm in early pregnancy. The fetus showed an early state of mummification. Histologically, a multifocal mononuclear encephalitis, myocarditis and periportal hepatitis was present indicating a possible protozoal cause of abortion. Although immunohistologically, Neospora (N.) caninum antigen could not be demonstrated, N. caninum DNA was detected by Polymerase Chain Reaction (PCR) in brain, heart, liver and lung of the fetus. N. caninum DNA was extracted from the aborted fetus and the microsatellite marker MS10 was amplified by PCR and sequenced. The obtained MS10 microsatellite pattern has not been described in Germany yet. Nevertheless, the MS10 pattern was very similar to those reported for N. caninum isolated from dogs and cattle in Germany. Because of the histological pattern and extent of the lesions, neosporosis was suspected as the cause of fetal death and abortion. This case report describes for the first time transplacental transmission of N. caninum and abortion due to neosporosis in a tapir. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiac Involvement with Parasitic Infections

PubMed Central

Hidron, Alicia; Vogenthaler, Nicholas; Santos-Preciado, José I.; Rodriguez-Morales, Alfonso J.; Franco-Paredes, Carlos; Rassi, Anis

2010-01-01

Summary: Parasitic infections previously seen only in developing tropical settings can be currently diagnosed worldwide due to travel and population migration. Some parasites may directly or indirectly affect various anatomical structures of the heart, with infections manifested as myocarditis, pericarditis, pancarditis, or pulmonary hypertension. Thus, it has become quite relevant for clinicians in developed settings to consider parasitic infections in the differential diagnosis of myocardial and pericardial disease anywhere around the globe. Chagas' disease is by far the most important parasitic infection of the heart and one that it is currently considered a global parasitic infection due to the growing migration of populations from areas where these infections are highly endemic to settings where they are not endemic. Current advances in the treatment of African trypanosomiasis offer hope to prevent not only the neurological complications but also the frequently identified cardiac manifestations of this life-threatening parasitic infection. The lack of effective vaccines, optimal chemoprophylaxis, or evidence-based pharmacological therapies to control many of the parasitic diseases of the heart, in particular Chagas' disease, makes this disease one of the most important public health challenges of our time. PMID:20375355

Magnesium sulphate and (123)I-MIBG in pheochromocytoma: Two useful techniques for a complicated disease.

PubMed

Vendrell, M; Martín, N; Tejedor, A; Ortiz, J T; Muxí, À; Taurà, P

2016-01-01

Pheochromocytoma is a tumour of the chromaffin tissue. It may, through catecholamine release, have deleterious effects on myocardial structure. A 48-year-old woman with a history of hypertension and type II diabetes mellitus (ASA II) was diagnosed of pheochromocytoma-induced myocarditis, which caused severe cardiogenic shock, with an ejection fraction of 20%. Extreme blood pressure swings required aggressive therapy with vasoactive drugs (norepinephrine and dopamine) and an intra-aortic balloon pump, despite which severe haemodynamic instability persisted. Finally, the use of magnesium sulphate allowed for cardiovascular stabilization and weaning off vasoactive drugs prior to surgery. (123)I-metaiodobenzylguanidine scintigraphy helps not only to functionally confirm tumour tissue, but also to assess severity and prognosis of cardiac failure. Prognosis of pheochromocytoma-induced heart failure can be very poor. The use of these two well-known and relatively simple 'tools' for treatment and prognosis is a helpful option to keep in mind. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

[West Nile virus expanding in Europe].

PubMed

Reusken, Chantal B E M; van Maanen, C Kees; Martina, Byron E; Sonder, Gerard J B; van Gorp, Eric C M; Koopmans, Marion P G

2011-01-01

The areas of Europe in which West Nile virus (WNV)-transmission to humans is observed have expanded over the last few years, with endemic circulation amongst animals of southern Europe. This situation calls for heightened vigilance to the clinical presentation of WNV infection in humans. The average incubation period lasts 2-6 days. Of those infected, 20% will experience a mild, non-specific disease presentation such as high fever, headache, myalgia, possibly with rash and lymphadenopathy; <1% will develop severe neurological symptoms. Rare complications include: myelitis, optic neuritis, rhombencephalitis, polyradiculitis, myocarditis, pancreatitis and fulminant hepatitis. Clinicians should take WNV infection into consideration when making a differential diagnosis for such symptoms in patients who have returned from areas with potential virus circulation. Given the increase in the spread of WNV within Europe, this now holds true for continental travellers as well as those destined for the Americas, Africa and Asia. It is important to include the patient's travel history, clinical symptoms and any occurrences of vaccination against viruses causing Japanese encephalitis, tick-borne encephalitis and yellow fever into the diagnostic workup, as the antibodies against these diseases show cross-reactivity.

Leptospirosis Outbreak in Sri Lanka in 2008: Lessons for Assessing the Global Burden of Disease

PubMed Central

Agampodi, Suneth B.; Peacock, Sharon J.; Thevanesam, Vasanthi; Nugegoda, Danaseela B.; Smythe, Lee; Thaipadungpanit, Janjira; Craig, Scott B.; Burns, Mary Ann; Dohnt, Michael; Boonsilp, Siriphan; Senaratne, Thamarasi; Kumara, Athula; Palihawadana, Paba; Perera, Sahan; Vinetz, Joseph M.

2011-01-01

Global leptospirosis disease burden estimates are hampered by the lack of scientifically sound data from countries with probable high endemicity and limited diagnostic capacities. We describe the seroepidemiologic and clinical characteristics of the leptospirosis outbreak in 2008 in Sri Lanka. Definitive/presumptive case definitions proposed by the World Health Organization Leptospirosis Epidemiology Reference Group were used for case confirmation. Of the 404 possible cases, 155 were confirmed to have leptospirosis. Highest titers of patient seum samples reacted with serovars Pyrogenes (28.7%), Hardjo (18.8%), Javanica (11.5%), and Hebdomadis (11.5%). Sequencing of the 16S ribosomal DNA gene identified six infections: five with Leptospira interrogans and one with L. weilli. In this patient population, acute renal failure was the main complication (14.8%), followed by myocarditis (7.1%) and heart failure (3.9%). The case-fatality rate was 1.3%. This report strengthens the urgent need for increasing laboratory diagnostic capabilities to determine the causes of epidemic and endemic infectious diseases in Sri Lanka, a finding relevant to other tropical regions. PMID:21896807

Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis.

PubMed

Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta

2016-09-01

In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded.

Contemporary review on the pathogenesis of takotsubo syndrome: The heart shedding tears: Norepinephrine churn and foam at the cardiac sympathetic nerve terminals.

PubMed

Y-Hassan, Shams; De Palma, Rodney

2017-02-01

Takotsubo syndrome (TS), an increasingly recognized acute cardiac disease entity, is characterized by a unique pattern of circumferential and typically regional left ventricular wall motion abnormality resulting in a conspicuous transient ballooning of the left ventricle during systole. The mechanism of the disease remains elusive. However, the sudden onset of acute myocardial stunning in a systematic pattern extending beyond a coronary artery territory; the history of a preceding emotional or physical stress factor in two thirds of cases; the signs of sympathetic denervation at the regions of left ventricular dysfunction on sympathetic scintigraphy; the finding of myocardial edema and other signs consistent with (catecholamine-induced) myocarditis shown by cardiac magnetic resonance imaging; and the contraction band necrosis on histopathological examination all argue strongly for the involvement of the cardiac sympathetic nervous system in the pathogenesis of TS. In this narrative review, extensive evidence in support of local cardiac sympathetic nerve hyperactivation, disruption and norepinephrine spillover causing TS in predisposed patients is provided. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Myocardial late gadolinium enhancement in specific cardiomyopathies by cardiovascular magnetic resonance: a preliminary experience.

PubMed

Silva, Caterina; Moon, James C; Elkington, Andrew G; John, Anna S; Mohiaddin, Raad H; Pennell, Dudley J

2007-12-01

Late gadolinium enhancement cardiovascular magnetic resonance (CMR) can visualize myocardial interstitial abnormalities. The aim of this study was to assess whether regions of abnormal myocardium can also be visualized by late enhancement gadolinium CMR in the specific cardiomyopathies. A retrospective review of all referrals for gadolinium CMR with specific cardiomyopathy over 20 months. Nine patients with different specific cardiomyopathies were identified. Late enhancement was demonstrated in all patients, with a mean signal intensity of 390 +/- 220% compared with normal regions. The distribution pattern of late enhancement was unlike the subendocardial late enhancement related to coronary territories found in myocardial infarction. The affected areas included papillary muscles (sarcoid), the mid-myocardium (Anderson-Fabry disease, glycogen storage disease, myocarditis, Becker muscular dystrophy) and the global sub-endocardium (systemic sclerosis, Loeffler's endocarditis, amyloid, Churg-Strauss). Focal myocardial late gadolinium enhancement is found in the specific cardiomyopathies, and the pattern is distinct from that seen in infarction. Further systematic studies are warranted to assess whether the pattern and extent of late enhancement may aid diagnosis and prognostic assessment.

Raptor mortality due to West Nile virus in the United States, 2002

USGS Publications Warehouse

Saito, E.K.; Sileo, L.; Green, D.E.; Meteyer, C.U.; McLaughlin, G.S.; Converse, K.A.; Docherty, D.E.

2007-01-01

West Nile virus (WNV) has affected many thousands of birds since it was first detected in North America in 1999, but the overall impact on wild bird populations is unknown. In mid-August 2002, wildlife rehabilitators and local wildlife officials from multiple states began reporting increasing numbers of sick and dying raptors, mostly red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus. Commonly reported clinical signs were nonspecific and included emaciation, lethargy, weakness, inability to perch, fly or stand, and nonresponse to danger. Raptor carcasses from 12 states were received, and diagnostic evaluation of 56 raptors implicated WNV infection in 40 (71%) of these cases. Histologically, nonsuppurative encephalitis and myocarditis were the salient lesions (79% and 61%, respectively). Other causes of death included lead poisoning, trauma, aspergillosis, and Salmonella spp. and Clostridium spp. infections. The reason(s) for the reported increase in raptor mortality due to WNV in 2002 compared with the previous WNV seasons is unclear, and a better understanding of the epizootiology and pathogenesis of the virus in raptor populations is needed. ?? Wildlife Disease Association 2007.

Lethal endomyocarditis caused by chronic "Krokodil" intoxication.

PubMed

Sorrentino, Antonella; Trotta, Silvia; Colucci, Anna Pia; Aventaggiato, Lucia; Marzullo, Andrea; Solarino, Biagio

2018-03-19

"Krokodil" is a home-made opioid drug obtained by synthesizing desomorphine from codeine and combining it with other low-cost additives. Initially introduced in the former Soviet countries, it was then imported to Western Europe as a heroin substitute. To our knowledge, this is the first report of an Italian case of lethal krokodil abuse, that occurred in a 39-year-old man, who died suddenly after transportation to the Emergency Department (ED) for hyperthermia associated with sweating, dyspnoea and tachycardia. Post-mortem examination revealed extensive necrotic ulcerative lesions on the forearms, and autopsy showed a hypertrophic heart with ample endocardial vegetation on the aortic valve and patency of the foramen ovale. Histopathological examination of the heart showed ulcero-vegetative lesions of the aortic valve with an abscess on the annulus and extension to the periaortic adipose tissue, as well as diffuse myocardial interstitial inflammatory neutrophilic infiltrates. Toxicological analysis demonstrated a desomorphine metabolite in urine. On the basis of all these findings the cause of death was ruled to be congestive heart failure caused by endocarditis and myocarditis, correlated with chronic abuse of krokodil.

Is a multivalent hand, foot, and mouth disease vaccine feasible?

PubMed Central

Klein, Michel; Chong, Pele

2015-01-01

Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed. PMID:26009802

[Effect of imidapril on the effective refractory period and sodium current of ventricular noninfarction zone in healed myocardial infarction].

PubMed

Li, Yang; Niu, Hui-Yan; Liu, Nian; Zhang, Cun-Tai; Lu, Zai-Ying; Wang, Shi-Wen

2005-07-01

To investigate the effects of imidapril (IMI) on effective refractory period (ERP) and sodium current (I(Na)) of myocytes in ventricular noninfarction zone of healed myocardial infarction (HMI) in rabbit models. Rabbits with left coronary artery ligation were prepared and IMI (0.625 mg x kg(-1) x d(-1), 8 weeks) was orally administered. The ERP and sodium current were recorded. The ERP in HMI heart was prolonged. The ERP in IMI group was lower significantly than that of HMI group. The I(Na) density of myocyte in HMI ventricle decreased obviously. V 1/2 of steady state inactivation of I(Na) shifted to hyperpolarization, and time constant (tau) of recovery from inactivation in HMI ventricular myocyte was longer than that of sham ventricular myocyte. I(Na) density in IMI group increased markedly as compared with that of HMI group. IMI was shown to reverse the abnormal prolongation of ERP in rabbit heart with the HMI and increase I(Na) density. It may be the mechanism of IMI preventing against antiarrhythmia in healed myocardical infarction.

Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review.

PubMed

Gao, Jialiang; Chen, Guang; He, Haoqiang; Liu, Chao; Xiong, Xingjiang; Li, Jun; Wang, Jie

2017-01-01

Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz. , containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply. Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, anticoagulation, antithrombosis, endothelial protection, myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction. In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for cardiovascular diseases (CVDs) including coronary heart disease, myocardial infarction, hypertension, atrial fibrillation, hyperlipidaemia, viral myocarditis, chronic heart failure, and pulmonary heart disease. However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications.

Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review

PubMed Central

Gao, Jialiang; Chen, Guang; He, Haoqiang; Liu, Chao; Xiong, Xingjiang; Li, Jun; Wang, Jie

2017-01-01

Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz., containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply. Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, anticoagulation, antithrombosis, endothelial protection, myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction. In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for cardiovascular diseases (CVDs) including coronary heart disease, myocardial infarction, hypertension, atrial fibrillation, hyperlipidaemia, viral myocarditis, chronic heart failure, and pulmonary heart disease. However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications. PMID:28588491

Lesions of neonatally induced toxoplasmosis in cats.

PubMed

Dubey, J P; Mattix, M E; Lipscomb, T P

1996-05-01

Five pregnant queens were inoculated orally with Toxoplasma gondii tissue cysts. Twenty-two live and three dead kittens were born 16 to 31 days after inoculation. Four kittens were eaten by queens and, thus, were not available for histologic examination. Twenty-one kittens that died or were euthanatized on day 2 (two kittens), 4 (one kitten), 5 (five kittens), 6 (five kittens), 7 (one kitten), 8 (four kittens), 16 (two kittens), and 29 (one kitten) after birth were studied histologically. T gondii was detected by bioassay and was seen in histologic sections of tissues from all 21 kittens. The histologic lesions associated with neonatal toxoplasmosis were widely disseminated infiltrates of macrophages and neutrophils often accompanied by necrosis; lymphocytes and plasma cells were occasionally present. The most consistent lesions were proliferative interstitial pneumonia (21/21); necrotizing hepatitis (20/21); myocarditis (21/21); skeletal myositis (21/21); glossal myositis (19/19); nonsuppurative encephalitis affecting the cerebrum (18/18), brain stem (15/15), and spinal cord (9/9); uveitis (19/19); necrotizing adrenal adenitis (18/18); and interstitial nephritis (16/21). Placental lesions (2/2) consisted of grossly visible areas of necrosis and mineralization.

Late Detection of Left Ventricular Dysfunction Using Two-Dimensional and Three-Dimensional Speckle-Tracking Echocardiography in Patients with History of Nonsevere Acute Myocarditis.

PubMed

Caspar, Thibault; Fichot, Marie; Ohana, Mickaël; El Ghannudi, Soraya; Morel, Olivier; Ohlmann, Patrick

2017-08-01

Acute myocarditis (AM) often involves the left ventricular (LV) subepicardium that might be displayed by cardiac magnetic resonance even late after the acute phase. In the absence of global or regional LV dysfunction, conventional transthoracic echocardiography (TTE) does not accurately identify tissue sequelae of AM. We sought to evaluate the diagnostic value of two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography to identify patients with a history of AM with preserved LV ejection fraction (LVEF). Fifty patients (group 1: age, 31.4 ± 10.5 years; 76% males) with a history of cardiac magnetic resonance-confirmed diagnosis of AM (according to the Lake Louise criteria) were retrospectively identified and then (21.7 ± 23.4 months later) evaluated by complete echocardiography including 2D and 3D speckle-tracking analysis, as well as 50 age- and gender-matched healthy controls (group 2: age, 31.2 ± 9.5 years: 76% males). Patients with a history of severe clinical presentation of AM (sudden death, ventricular arrhythmia, heart failure, alteration of LVEF) were excluded. At diagnosis, peak troponin and C-reactive protein were 11.97 (interquartile range, 4.52-25.92) μg/L and 32.3 (interquartile range, 14.85-70.45) mg/L, respectively. Mean delay between acute phase and follow-up study TTE was 21.7 ± 23.4 months. LVEF was not statistically different between groups (62.1% vs 63.5%, P = .099). Two-dimensional global longitudinal strain (GLS) was lower in magnitude in group 1 (-17.8% vs -22.1%, P < .0001) as were 2D layer-specific subepicardial GLS (-15.4% vs -19.7%, P < .0001) and subendocardial GLS (-20.71% vs -25.08%, P < .0001). Three-dimensional global longitudinal, circumferential, area, and radial strains were lower in magnitude in group 1 (-11.80% vs -14.98%, P < .0001; -12.57% vs -15.12%, P < .0001; -22.28% vs -25.87%, P < .0001; 31.47% vs 38.06%, P < .0001, respectively). Receiver operating characteristic curve analysis showed that subepicardial GLS displayed a better diagnostic performance to detect sequelae of AM as compared with GLS (area under the curve = 0.97 vs 0.93, P = .045). In patients with a history of AM, a subtle LV dysfunction can be detected by 2D and 3D speckle-tracking echocardiography, even though LVEF is conserved, adding incremental information over conventional TTE. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Fatal Disseminated Toxoplasma gondii Infection in a Captive Harbour Porpoise (Phocoena phocoena).

PubMed

Herder, V; van de Velde, N; Højer Kristensen, J; van Elk, C; Peters, M; Kilwinski, J; Schares, G; Siebert, U; Wohlsein, P

2015-11-01

A 7-year-old female harbour porpoise (Phocoena phocoena), born and held in captivity, suffered from reduced consciousness, imprecise and circling swimming movements and long phases of immobility over a period of 3 weeks. The animal died during treatment in a Danish open sea facility. Pathological examination revealed multifocal pyogranulomatous to necrotizing meningoencephalomyelitis, ganglioneuritis, plexus chorioiditis, myocarditis, hepatitis and adrenalitis with few intralesional protozoal tachyzoites and bradyzoites within cysts. Immunohistochemistry was positive for Toxoplasma gondii antigen within the lesions. Using polymerase chain reaction (PCR), the presence of T. gondii-specific genome fragments was confirmed. A multilocus PCR-restriction fragment length polymorphism analysis using nine unlinked marker regions (nSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) resulted in the identification of T. gondii type II (variant Apico Type I), which is the T. gondii genotype dominating in Germany. This is the first description of disseminated fatal toxoplasmosis in a captive harbour porpoise that lived in an open sea basin. Surface water contaminated with toxoplasma oocysts is regarded as the most likely source of infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that Bind Estrogen Receptors

PubMed Central

Ye, Hao; Ng, Hui Wen; Sakkiah, Sugunadevi; Ge, Weigong; Perkins, Roger; Tong, Weida; Hong, Huixiao

2016-01-01

Flavonoids are frequently used as dietary supplements in the absence of research evidence regarding health benefits or toxicity. Furthermore, ingested doses could far exceed those received from diet in the course of normal living. Some flavonoids exhibit binding to estrogen receptors (ERs) with consequential vigilance by regulatory authorities at the U.S. EPA and FDA. Regulatory authorities must consider both beneficial claims and potential adverse effects, warranting the increases in research that has spanned almost two decades. Here, we report pathway enrichment of 14 targets from the Comparative Toxicogenomics Database (CTD) and the Herbal Ingredients’ Targets (HIT) database for 22 flavonoids that bind ERs. The selected flavonoids are confirmed ER binders from our earlier studies, and were here found in mainly involved in three types of biological processes, ER regulation, estrogen metabolism and synthesis, and apoptosis. Besides cancers, we conjecture that the flavonoids may affect several diseases via apoptosis pathways. Diseases such as amyotrophic lateral sclerosis, viral myocarditis and non-alcoholic fatty liver disease could be implicated. More generally, apoptosis processes may be importantly evolved biological functions of flavonoids that bind ERs and high dose ingestion of those flavonoids could adversely disrupt the cellular apoptosis process. PMID:27023590

Medico-legal perspectives on sudden cardiac death in young athletes.

PubMed

Oliva, Antonio; Grassi, Vincenzo M; Campuzano, Oscar; Brion, Maria; Arena, Vincenzo; Partemi, Sara; Coll, Monica; Pascali, Vincenzo L; Brugada, Josep; Carracedo, Angel; Brugada, Ramon

2017-03-01

Sudden cardiac death (SCD) in a young athlete represents a dramatic event, and an increasing number of medico-legal cases have addressed this topic. In addition to representing an ethical and medico-legal responsibility, prevention of SCD is directly correlated with accurate eligibility/disqualification decisions, with an inappropriate pronouncement in either direction potentially leading to legal controversy. This review summarizes the common causes of SCD in young athletes, divided into structural (hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, congenital coronary artery anomalies, etc.), electrical (Brugada, congenital LQT, Wolf-Parkinson-White syndrome, etc.), and acquired cardiac abnormalities (myocarditis, etc.). In addition, the roles of hereditary cardiac anomalies in SCD in athletes and the effects of a positive result on them and their families are discussed. The medico-legal relevance of pre-participation screening is analyzed, and recommendations from the American Heart Association and European Society of Cardiology are compared. Finally, the main issues concerning the differentiation between physiologic cardiac adaptation in athletes and pathologic findings and, thereby, definition of the so-called gray zone, which is based on exact knowledge of the mechanism of cardiac remodeling including structural or functional adaptions, will be addressed.

Lyme Carditis Buried Beneath ST-Segment Elevations

PubMed Central

Umpierrez De Reguero, Adrian

2017-01-01

Lyme disease is caused by the spirochete Borrelia burgdorferi and is carried to human hosts by infected ticks. There are nearly 30,000 cases of Lyme disease reported to the CDC each year, with 3-4% of those cases reporting Lyme carditis. The most common manifestation of Lyme carditis is partial heart block following bacterial-induced inflammation of the conducting nodes. Here we report a 45-year-old gentleman that presented to the hospital with intense nonradiating chest pressure and tightness. Lab studies were remarkable for elevated troponins. EKG demonstrated normal sinus rhythm with mild ST elevations. Three weeks prior to hospital presentation, patient had gone hunting near Madison. One week prior to admission, he noticed an erythematous lesion on his right shoulder. Because of his constellation of history, arthralgias, and carditis, he was started on ceftriaxone to treat probable Lyme disease. This case illustrates the importance of thorough history taking and extensive physical examination when assessing a case of possible acute myocardial infarction. Because Lyme carditis is reversible, recognition of this syndrome in young patients, whether in the form of AV block, myocarditis, or acute myocardial ischemia, is critical to the initiation of appropriate antibiotics in order to prevent permanent heart block, or even death. PMID:28713599

COULD INTERFERON-GAMMA BE A THERAPEUTIC TARGET FOR TREATING HEART FAILURE?

PubMed Central

Levick, Scott P.; Goldspink, Paul H.

2013-01-01

The cytokine interferon-gamma (IFN-γ), is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. Whilst a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will: 1) discuss the source of IFN-γ in the diseased heart; 2) summarize the data from animal studies; 3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; 4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and 5) present the clinical evidence supporting a role for IFN-γ in heart failure. PMID:23589353

Amdoparvovirus Infection in Red Pandas ( Ailurus fulgens).

PubMed

Alex, Charles E; Kubiski, Steven V; Li, Linlin; Sadeghi, Mohammadreza; Wack, Raymund F; McCarthy, Megan A; Pesavento, Joseph B; Delwart, Eric; Pesavento, Patricia A

2018-01-01

Aleutian mink disease virus is the type species in the genus Amdoparvovirus, and in mink and other Mustelidae can cause either subclinical disease or fatal chronic immune stimulation and immune complex disease. The authors describe a novel amdoparvovirus in the endangered red panda ( Ailurus fulgens), discovered using viral metagenomics. The authors analyzed the prevalence, tissue distribution, and disease association by PCR, in situ hybridization, electron microscopy, and histology in a group of 6 red pandas from a single zoological collection. The study incorporates a fecal shedding survey and analysis of tissues from 4 necropsied animals over a 12-year span. The tentatively named red panda amdoparvovirus (RpAPV) was detected in the feces and/or tissues of all animals tested. At necropsy of 1 geriatric animal, infection was associated with pyogranulomatous peritonitis, pancreatitis, and myocarditis. Other animals had detectable low-level viral nucleic acid in lymph nodes and both oral and intestinal epithelium at the time of necropsy. Full-length genome sequences of RpAPV strains from 2 animals had 12% sequence divergence, demonstrating genetic diversity even among in-contact animals. RpAPV is a persistent infection in this cohort of red pandas, and has variable clinical expression.

An outbreak of sarcocystosis in psittacines and a pigeon in a zoological collection in Brazil.

PubMed

Ecco, R; Luppi, M M; Malta, M C C; Araújo, M R; Guedes, R M C; Shivaprasad, H L

2008-12-01

This report describes an outbreak of acute pulmonary sarcocystosis in different species of captive psittacines and in a Luzon bleeding-heart pigeon (Gallicolumba luzonica) in a zoological collection in Brazil. A majority of the birds were found dead and had exhibited no previous clinical signs. Grossly, pulmonary congestion and edema were the most-common findings. Enlarged and congested livers and spleens were also frequently observed. Microscopically, there was edema, fibrin exudation, congestion, and perivascular and interstitial lymphoplasmacytic infiltration associated with numerous sinuous schizonts of Sarcocystis sp. in the lungs. Mild to moderate myocarditis, hepatitis, splenitis, and interstitial nephritis were also observed in the birds. Immunohistochemistry confirmed Sarcocystis sp. in the capillaries of lungs, hearts, livers, and spleens of most of the birds, but also in the pancreas, kidney, intestine, proventriculus, and brain of a few birds. The probable source of Sarcocystis sp. in these birds was the wild opossum (Didelphis albiventris), a common inhabitant of a local forest that surrounds the Belo Horizonte Zoo (Fundação Zoo-Botânica). This is the first documentation of Sarcocystis infection in psittacines and a pigeon from Brazil.

Congestive heart failure in subjects with thyrotoxicosis in a black community

PubMed Central

Anakwue, R C; Onwubere, B J C; Anisiuba, B C; Ikeh, V O; Mbah, A; Ike, S O

2010-01-01

Introduction: Thyroid hormone has profound effects on a number of metabolic processes in virtually all tissues but the cardiovascular manifestations are prominent usually creating a hyperdynamic circulatory state. Thyrotoxicosis is not a common cause of congestive heart failure among black communities. Objectives: To determine the hospital prevalence, clinical characteristics and echocardiographic findings in patients with thyrotoxicosis who present with congestive heart failure (CCF) in the eastern part of Nigeria. Subjects and methods: A total of 50 subjects aged 15 years and above who were diagnosed as thyrotoxic following clinical and thyroid function tests were consecutively recruited. Fifty age- and sex-matched controls with no clinical or biochemical evidence of thyrotoxicosis and no comorbidities were used as controls. Two-dimensional echocardiography was carried out on all the subjects. CCF was determined clinically and echocardiographically. Results: Eight patients (5 females and 3 males) out of a total of 50 thyrotoxic patients presented with congestive heart failure. Conclusion: The study revealed that congestive heart failure can occur in thyrotoxicosis in spite of the associated hyperdynamic condition. The underlying mechanism may include direct damage by autoimmune myocarditis, congestive circulation secondary to excess sodium, and fluid retention. PMID:20730063

Rare and very rare adverse effects of clozapine

PubMed Central

De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

2015-01-01

Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

Histophilus somni host-parasite relationships.

PubMed

Corbeil, Lynette B

2007-12-01

Histophilus somni (Haemophilus somnus) is one of the key bacterial pathogens involved in the multifactorial etiology of the Bovine Respiratory Disease Complex. This Gram negative pleomorphic rod also causes bovine septicemia, thrombotic meningencephalitis, myocarditis, arthritis, abortion and infertility, as well as disease in sheep, bison and bighorn sheep. Virulence factors include lipooligosaccharide, immunoglobulin binding proteins (as a surface fibrillar network), a major outer membrane protein (MOMP), other outer membrane proteins (OMPs) and exopolysaccharide. Histamine production, biofilm formation and quorum sensing may also contribute to pathogenesis. Antibodies are very important in protection as shown in passive protection studies. The lack of long-term survival of the organism in macrophages, unlike facultative intracellular bacteria, also suggests that antibodies should be critical in protection. Of the immunoglobulin classes, IgG2 antibodies are most implicated in protection and IgE antibodies in immunopathogenesis. The immunodominant antigen recognized by IgE is the MOMP and by IgG2 is a 40 kDa OMP. Pathogenetic synergy of bovine respiratory syncytial virus (BRSV) and H. somni in calves can be attributed, in part at least, to the higher IgE anti-MOMP antibody responses in dually infected calves. Other antigens are probably involved in stimulating host defense or immunopathology as well.

Prevalence and Pathology of West Nile Virus in Naturally Infected House Sparrows, Western Nebraska, 2008

PubMed Central

O'Brien, Valerie A.; Meteyer, Carol U.; Reisen, William K.; Ip, Hon S.; Brown, Charles R.

2010-01-01

Nestling birds are rarely sampled in the field for most arboviruses, yet they may be important in arbovirus amplification cycles. We sampled both nestling and adult house sparrows (Passer domesticus) in western Nebraska for West Nile virus (WNV) or WNV-specific antibodies throughout the summer of 2008 and describe pathology in naturally infected nestlings. Across the summer, 4% of nestling house sparrows were WNV-positive; for the month of August alone, 12.3% were positive. Two WNV-positive nestlings exhibited encephalitis, splenomegaly, hepatic necrosis, nephrosis, and myocarditis. One nestling sparrow had large mural thrombi in the atria and ventricle and immunohistochemical staining of WNV antigen in multiple organs including the wall of the aorta and pulmonary artery; cardiac insufficiency thus may have been a cause of death. Adult house sparrows showed an overall seroprevalence of 13.8% that did not change significantly across the summer months. The WNV-positive nestlings and the majority of seropositive adults were detected within separate spatial clusters. Nestling birds, especially those reared late in the summer when WNV activity is typically greatest, may be important in virus amplification. PMID:20439979

High mortality and lesions of the central nervous system in trypanosomosis by Trypanosoma vivax in Brazilian hair sheep.

PubMed

Galiza, G J N; Garcia, H A; Assis, A C O; Oliveira, D M; Pimentel, L A; Dantas, A F M; Simões, S V D; Teixeira, M M G; Riet-Correa, F

2011-12-15

Here, we report an outbreak of Trypanosoma vivax-induced trypanosomosis in Brazilian hair sheep on a farm in Paraíba state, a non-endemic region in northeastern Brazilian. Of 306 total sheep, 240 showed clinical signs and 216 died. Clinical signs included anorexia, lethargy, anemia, rough hair coat, weight loss, submandibular edema, abortion, and in some cases, neurological signs such as head pressing, lateral recumbence, paddling movements and muscle tremors. T. vivax was identified by blood smear analysis and polymerase chain reaction (PCR). At necropsy, animals exhibited watery blood, pale tissue coloring, and the presence of liquid in the peritoneal cavity and pericardial sac. Histologically, nonsuppurative myocarditis and meningoencephalitis with areas of malacia were observed. After treatment, no parasites were detected by blood smear analysis or PCR. Cattle and buffalo that remained in the same pasture were also infected but presented with asymptomatic infections. Epidemiological data suggest that T. vivax was introduced to the farm and the susceptible flock by buffalos that were asymptomatic carriers of the infection; T. vivax was most likely transmitted by Tabanus spp. bites and also iatrogenically. Copyright © 2011 Elsevier B.V. All rights reserved.

Lyme borreliosis: ten years after discovery of the etiologic agent, Borrelia burgdorferi.

PubMed

Burgdorfer, W

1991-01-01

Since the recovery of its causative agent, Borrelia burgdorferi, in 1981, Lyme borreliosis has become the most prevalent tick-borne disease in the United States as well as in Europe. Its steadily increasing clinical spectrum now includes erythema migrans, acrodermatitis chronica atrophicans, lymphadenosis beniga cutis, arthritis, myocarditis, progressive meningoencephalitis, myositis, and various ocular and skin disorders. The true incidence of Lyme borreliosis in the world is unknown. In the United States, it has increased from 2,000 cases in 1987, to more than 8,000 in 1989. It occurs now in regions where the tick vectors, Ixodes dammini and Ixodes pacificus, are absent and where other species of ticks may be responsible for maintaining and distributing the spirochete. In Europe, Lyme borreliosis has been reported from 19 countries; its occurrence coincides with the distribution of the vector tick, Ixodes ricinus and possibly Ixodes hexagonus. Specific and dependable serological tests are still not available, but development of probes for specific antigens and the polymerase chain reaction appear promising in detecting ongoing infections and in identifying B. burgdorferi in ticks, animal, and human hosts. Brief reference is made to advances in the preparation of whole cell and genetically engineered vaccines.

A clinical approach to Lyme disease.

PubMed

Nadelman, R B; Wormser, G P

1990-05-01

Lyme disease (also known as Lyme borreliosis) is an emerging, newly described infectious disease with diverse clinical manifestations. The disease is caused by the spirochetal agent Borrelia burgdorferi, which is transmitted to humans by the bite of certain species of Ixodes ticks harboring the organism. The most readily identifiable clinical feature is the distinctive skin lesion, erythema migrans. If recently infected patients go untreated, approximately 15% will develop neurologic conditions (most commonly facial nerve palsy), 8% will develop myocarditis (typically with heart block), and 60% will develop migratory mono- or pauci-articular arthritis. Diagnosis depends on clinical suspicion, recognition of the characteristic signs and symptoms, and appropriate testing for antibody to B. burgdorferi. Serology for Lyme disease, although in need of better standardization, is most useful in diagnosing patients with manifestations of Lyme disease other than erythema migrans. All manifestations of Lyme disease are potentially treatable with either a beta-lactam antibiotic (for instance penicillin, amoxicillin, or ceftriaxone) or a tetracycline preparation. However, the optimal antimicrobial regimen, including choice of drug, drug dose, route of administration, and length of therapy, is unknown. Other important areas for future research include Ixodes biology and control, improved laboratory tests for diagnosis and for assessing response to therapy, and vaccine development.

[Parvovirus B19 infection after kidney transplantation].

PubMed

Brodin-Sartorius, Albane; Mekki, Yahia; Bloquel, Bénédicte; Rabant, Marion; Legendre, Christophe

2012-02-01

Prevalence for human parvovirus B19 infection is estimated to be between 2% and 30% in renal transplant recipients. In post-transplant settings, parvovirus B19 infection may occur either as a primary infection or a reactivation. Parvovirus transmission most commonly occurs through respiratory tract but may also result from graft or blood packs contamination. Co-infections with HHV-6 and CMV viruses are frequent. The hallmark symptom is anemia, more rarely pancytopenia and hemophagocytic syndrome. In respect to renal involvement, parvovirus B19 infection has been associated with graft dysfunction in 10% of cases. Both thrombotic microangiopathies and collapsing glomerulopathies have been reported concomitantly with parvovirus B19 infection but the causal link remains unclear. Other complications are seldomly reported, including hepatitis, encephalitis, and myocarditis. Diagnosis is based on pre and post-transplant serological status. In addition, the management of parvovirus B19 infection in immunocompromised patients requires quantitative assessment of blood viral load by PCR. The treatment relies primarily on reduction of immunosuppression combined with intravenous immunoglobulin infusions. Relapses occur in 30% of cases. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Chagas Cardiomyopathy in New Orleans and the Southeastern United States.

PubMed

Hsu, Robert C; Burak, Joshua; Tiwari, Sumit; Chakraborti, Chayan; Sander, Gary E

2016-01-01

Chagas disease (CD), caused by Trypanosoma cruzi, affects 6-7 million people worldwide annually, primarily in Central and South America, and >300,000 people in the United States. CD consists of acute and chronic stages. Hallmarks of acute CD include fever, myalgia, diaphoresis, hepatosplenomegaly, and myocarditis. Symptoms of chronic CD include pathologic involvement of the heart, esophagus, and colon. Myocardial involvement is identifiable by electrocardiogram and cardiac magnetic resonance imaging showing inflammation and left ventricular wall functional abnormalities. We present two cases of CD identified in a single hospital in the Southeastern United States. Case 1 presents a patient with symptoms of anginal chest pain and associated shortness of breath with myocardial involvement suggestive of ischemic infarction but normal coronary arteries. Case 2 describes a patient with no physical symptoms and echocardiogram with ejection fraction of 50% with posterolateral and anterolateral wall hypokinesis but normal coronary arteries. With a growing number of immigrants from Central and South America in the United States, it is imperative for clinicians to include CD as part of the differential diagnosis for patients presenting with heart disease who have a history of exposure to T. cruzi endemic areas.

Distribution of late gadolinium enhancement in various types of cardiomyopathies: Significance in differential diagnosis, clinical features and prognosis.

PubMed

Satoh, Hiroshi; Sano, Makoto; Suwa, Kenichiro; Saitoh, Takeji; Nobuhara, Mamoru; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Hayashi, Hideharu

2014-07-26

The recent development of cardiac magnetic resonance (CMR) techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution. We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies (ICM and NICM), especially in terms of the location and distribution of late gadolinium enhancement (LGE). CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory, and the subendocardial or transmural LGE. LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer. The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function, including dilated cardiomyopathy, end-stage hypertrophic cardiomyopathy (HCM), cardiac sarcoidosis, and myocarditis, and those with diffuse left ventricular (LV) hypertrophy including HCM, cardiac amyloidosis and Anderson-Fabry disease. A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy. In arrhythmogenic right ventricular cardiomyopathy/dysplasia, an enhancement of right ventricular (RV) wall with functional and morphological changes of RV becomes apparent. Finally, the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments.

Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification.

PubMed

Krasota, Alexandr; Loginovskih, Natalia; Ivanova, Olga; Lipskaya, Galina

2016-01-06

Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.

Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification

PubMed Central

Krasota, Alexandr; Loginovskih, Natalia; Ivanova, Olga; Lipskaya, Galina

2016-01-01

Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF. PMID:26751470

Tissue tropism, pathology and pathogenesis of enterovirus infection.

PubMed

Muehlenbachs, Atis; Bhatnagar, Julu; Zaki, Sherif R

2015-01-01

Enteroviruses are very common and cause infections with a diverse array of clinical features. Enteroviruses are most frequently considered by practising pathologists in cases of aseptic meningitis, encephalitis, myocarditis and disseminated infections in neonates and infants. Congenital infections have been reported and transplacental transmission is thought to occur. Although skin biopsies during hand, foot and mouth disease are infrequently obtained, characteristic dermatopathological findings can be seen. Enteroviruses have been implicated in lower respiratory tract infections. This review highlights histopathological features of enterovirus infection and discusses diagnostic modalities for formalin-fixed paraffin-embedded tissues and their associated pitfalls. Immunohistochemistry can detect enterovirus antigen within cells of affected tissues; however, assays can be non-specific and detect other viruses. Molecular methods are increasingly relied upon but, due to the high frequency of asymptomatic enteroviral infections, clinical-pathological correlation is needed to determine significance. Of note, diagnostic assays on central nervous system or cardiac tissues from immunocompetent patients with prolonged disease courses are most often negative. Histopathological, immunohistochemical and molecular studies performed on clinical specimens also provide insight into enteroviral tissue tropism and pathogenesis. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Enterovirus and Parechovirus Surveillance - United States, 2014-2016.

PubMed

Abedi, Glen R; Watson, John T; Nix, W Allan; Oberste, M Steven; Gerber, Susan I

2018-05-11

Infections caused by enteroviruses (EV) and parechoviruses (PeV), members of the Picornaviridae family, are associated with various clinical manifestations, including hand, foot, and mouth disease; respiratory illness; myocarditis; meningitis; and sepsis; and can result in death. The genus Enterovirus includes four species of enterovirus (A-D) known to infect humans, and the genus Parechovirus includes one species (A) that infects humans. These species are further divided into types, some of which are associated with specific clinical manifestations. During 2014-2016, a total of 2,967 U.S. cases of EV and PeV infections were reported to the National Enterovirus Surveillance System (NESS). The largest number of reports during that time (2,051) occurred in 2014, when a large nationwide outbreak of enterovirus D68 (EV-D68) occurred, accounting for 68% of cases reported to NESS that year (1). Reports to the National Respiratory and Enteric Virus Surveillance System (NREVSS) during 2014-2016 indicated that circulation of EV peaks annually in the summer and early fall. Because the predominant types of EV and PeV circulating from year to year tend to vary, tracking these trends requires consistent and complete reports from laboratories with the capacity to perform typing.

Human immunodeficiency virus-associated heart failure in sub-Saharan Africa: evolution in the epidemiology, pathophysiology, and clinical manifestations in the antiretroviral era.

PubMed

Ntusi, Ntobeko A B; Ntsekhe, Mpiko

2016-09-01

The survival of patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) who have access to highly active antiretroviral therapy (ART) has dramatically increased in recent times. This review focuses on HIV-associated heart failure in sub-Saharan Africa (SSA). In HIV infected persons, heart failure may be related to pathology of the pericardium, the myocardium, the valves, the conduction system, or the coronary and pulmonary vasculature. HIV-associated heart failure can be because of direct consequences of HIV infection, autoimmune reactions, pro-inflammatory cytokines, opportunistic infections (OIs) or neoplasms, use of ART or therapy for OIs and presence of traditional cardiovascular risk factors. Myocardial involvement includes diastolic dysfunction, asymptomatic left ventricular dysfunction, cardiomyopathy, myocarditis, fibrosis, and steatosis. Pericardial diseases include pericarditis, pericardial effusions (rarely causing tamponade), pericardial constriction, and effusive-constrictive syndromes. Coronary artery disease is commonly reported in industrial nations, although its prevalence is thought to be low in HIV-infected persons from SSA. © 2016 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Cardiac Troponins and Autoimmunity: their role in the pathogenesis of myocarditis and of heart failure

PubMed Central

Kaya, Ziya; Katus, Hugo A.; Rose, Noel R.

2010-01-01

Despite the widespread use of cardiac troponins as biomarkers for the diagnosis and quantitation of cardiac injury, the effect of troponin release and a possible autoimmune response to the troponins is unknown. Other investigators reported that programmed cell death – 1 (PD-1) – receptor deficient mice developed severe cardiomyopathy with autoantibodies to troponin I. We found that immunization of genetically susceptible mice with troponin I but not troponin T induced a robust autoimmune response leading to marked inflammation and fibrosis in the myocardium. At later times, antibodies to cardiac myosin were detected in troponin – immunized mice. The severity of inflammation correlated with expression of chemokines RANTES, MIP-2, IP-10 and MCD-1 in the myocardium. Prior immunization with troponin I increased the severity of experimental infarctions, indicating that an autoimmune response to troponin I aggravates acute cardiac damage. Cardiac inflammation, fibrosis and functional impairment were transferred from immunized to naive recipients by CD4+ T cells, and the cytokine profile suggested both a Th2 and Th17 profile in A/J mice. Finally we identified an 18-mer of troponin I containing an immuno-dominant epitope. PMID:19446498

Q fever: a contemporary case series from a Belgian hospital.

PubMed

Vanderbeke, Lore; Peetermans, Willy E; Saegeman, Veroniek; De Munter, Paul

2016-04-27

Q fever is a global zoonosis that can cause both acute and chronic infections in humans through aerogenic transmission. Although Q fever was discovered already 80 years ago, this infectious disease remains largely unknown. We studied a case series in a Belgian tertiary care hospital. A laboratory and file query at our department was performed to detect patients who were newly diagnosed with Q fever from 01 January 2005 to 01 October 2014. In total, 10 acute Q fever and 5 chronic Q fever infections were identified. An aspecific flu-like illness was the prevailing manifestation of acute Q fever, while this was infective endocarditis in chronic Q fever cases. Noteworthy are the high percentage of myocarditis cases in the acute setting and one case of amyloidosis as a manifestation of chronic Q fever. No evolution from acute to chronic Q fever was noted; overall outcome for both acute and chronic Q fever was favourable with a 94% survival rate. Q fever is an infectious disease characterised by a variable clinical presentation. Detection requires correct assessment of the clinical picture in combination with a laboratory confirmation. Treatment and follow-up are intended to avoid a negative outcome.

Automated laser spectrofluorimeter for monitoring of myocardial metabolism

NASA Astrophysics Data System (ADS)

Popov, A. Yu.; Salmin, V. V.; Fursov, A. A.; Stepanenko, A. V.; Sokolovich, A. G.; Salmina, A. B.; Rebenkova, A. A.; Makarov, R. A.; Provorov, A. S.

2006-09-01

Methods of optical biopsy have a series of advantages before other methods of clinical diagnostics. The high accuracy of received results enables registration even small change of concentration of substances, and the opportunity of remote registration makes methods optical biopsy by an optimum means for noninvasive methods of diagnostics in medicine. The method of the fluorescent analysis allows to investigate dynamics of changes of a functional condition of organs and tissue in norm and pathologies, called by the various factors (an inflammation, ischemia, degenerative changes). Bring the results of development of expiremental setup for the laser fluorescent analysis of physiological and functional condition of various organs and tissue of organism. In expiremental setup was used pulse UF nitric laser with length of wave generation = 337 nm. For delivery of radiation to tissue, and, also, collection of a radiation of fluorescence were used various optic fiber scheme. The expiremental setup includes automated tunable monochromator and ADC, receiving a signal from photomultiplier tube. Driving of all blocks and processing of results is realize on IBM-compatible computer with the appropriate software. Was used the synchronous detecting for reducing of a background signal. Myocard at surgical introoperation by an accompanied condition of sharp ischemia was researches on these expiremental setup. Spectrofluorimetric criteria of an estimation of a condition of viscus at peritonitis were development.

Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress.

PubMed

Xu, Jing; Pan, Shengchi; Gan, Fang; Hao, Shu; Liu, Dandan; Xu, Haibin; Huang, Kehe

2018-04-01

Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors contributing to Keshan disease. But the relationship among these three factors is poorly described. This study aims to explore whether selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism. Cardiomyocytes were isolated from neonatal rat and cultured at the physiological (2.0 μM) or lower concentrations of selenium with different concentrations of T-2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin-induced cardiomyocyte injury in a concentration-dependent manner as demonstrated by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3 protein expressions. T-2 toxin treatment significantly increased mRNA expressions for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control. Selenium deficiencies further promoted GRP78, CHOP and p-eIF2α expressions. Knockdown of CHOP by the specific small interfering RNA eliminated the effect of selenium deficiencies on T-2 toxin-induced injury. It could be concluded that selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through initiating more aggressive endoplasmic reticulum stress. Copyright © 2018 Elsevier B.V. All rights reserved.

[Toxocariasis under the present conditions].

PubMed

Uspenskiĭ, A V; Peshkov, R A; Gorokhov, V V; Gorokhova, E V

2011-01-01

Toxocariasis is today the most widespread zoonotic, helminthic infection in Russia and other countries of the world. A large population of Toxocara has recently inhabited the urban populations of dogs and cats. Therefore toxocariasis canis and toxocariasis cati have shifted from rural areas to cities and megalopolises where Toxocara canis infestation amounts to as much as 100%, without excluding that in the rural populations of dogs. Due to the fact that the number of dogs and cats has considerably increased (20% of adult dogs and 80% of puppies are infected with Toxocara) in our megalopolises, cities, and urban communities as in foreign countries, this substantially increases the risk of toxacariasis. From the above reasoning, environmental contamination with Toxacara eggs creates an important reservoir of infestation for humans and animals (the contamination rates in different regions of Russia ranges from 1-3 to 50-60%, with the infestation rates of 1 - 10 eggs per 100 g of soil). Human toxocariasis is polymorphic, from its subclinical course to significant organ pathology, and detectable as a manifestation of eosinophilia, fever, hepatomegaly, hyperglobulinemia, lung and central nervous system lesions, myocarditis, and skin rash. The diagnosis of toxocariasis is established by its clinical presentation and serological findings. It is important in the history that children have spent much time with dogs or cats.

American trypanosomiasis.

PubMed

Carod-Artal, Francisco Javier

2013-01-01

American trypanosomiasis is a parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. Chagas disease is endemic in Latin America, where an estimated 10-14 million people are infected, and an emerging disease in Europe and the USA. Trypanosoma cruzi is transmitted by blood-sucking bugs of the family Reduviidae. Rhodnius prolixus, Panstrongylus megistus, Triatoma infestans, and T. dimidiata are the main vectors in the sylvatic cycle. Non vector-borne transmission includes blood transfusion, congenital and oral transmission, transplantation, and accidental infections. Most cases of acute infection occur in childhood and are usually asymptomatic, although severe myocarditis and meningoencephalitis may occur. Approximately 30% of T. cruzi-infected people will develop the chronic stage of the disease. Chronic chagasic cardiomyopathy is characterized by progressive heart failure, arrhythmias, intraventricular conduction defects, sudden death, and peripheral thromboembolism. Acute exacerbation can occur in individuals with involvement of cellular immunity such as advanced AIDS (acquired immunodeficiency syndrome), and transplant-associated immunosuppression. Neurological involvement may present with encephalitis, meningoencephalitis, or a space-occupying cerebral lesion called chagoma. Chagas disease is a major cause of ischemic stroke in Latin America. Several epidemiological studies have found an association between T. cruzi infection and cardioembolic ischemic stroke. Benznidazole and nifurtimox are the two available trypanocide drugs against T. cruzi. Copyright © 2013 Elsevier B.V. All rights reserved.

Detection of human parvovirus B19 DNA in 22% of 1815 cutaneous biopsies of a wide variety of dermatological conditions suggests viral persistence after primary infection and casts doubts on its pathogenic significance.

PubMed

Santonja, C; Santos-Briz, A; Palmedo, G; Kutzner, H; Requena, L

2017-10-01

Human parvovirus B19 (B19V) has been associated with a number of dermatological and systemic conditions, including myocarditis and autoimmune syndromes. To determine the frequency of B19V DNA detection in a large dermatopathology practice, and to characterize the histopathological patterns involved. We selected for polymerase chain reaction (PCR) detection of B19V a total of 1815 skin biopsies pertaining to entities allegedly related to B19V, as well as cases suspected clinically of representing paraviral exanthemas. Immunohistochemical detection of B19V viral protein 2 (VP2) was performed in 92 PCR-positive cases. B19V DNA was found by PCR in 402 out of 1825 biopsy specimens (22%). VP2 protein was identified by immunohistochemistry in only three instances of papular purpuric 'gloves-and-socks' syndrome. As the virus has the capacity to persist in different tissues (including the skin) for long periods, it could represent merely an innocent bystander, so no pathogenetic significance can be inferred from the PCR positivity for B19V in the vast majority of dermatological conditions studied. © 2017 British Association of Dermatologists.

Trypanosoma cruzi Necrotizing Meningoencephalitis in a Venezuelan HIV+-AIDS Patient: Pathological Diagnosis Confirmed by PCR Using Formalin-Fixed- and Paraffin-Embedded-Tissues

PubMed Central

Rossi Spadafora, Marcello Salvatore; Céspedes, Ghislaine; Romero, Sandra; Fuentes, Isabel; Boada-Sucre, Alpidio A.; Cañavate, Carmen; Flores-Chávez, María

2014-01-01

Coinfections with human immunodeficiency virus (HIV) and infectious agents have been recognized since the early 90s. In the central nervous system (CNS) of HIV+ patients, parasitic protozoans like Toxoplasma gondii have been described as responsible for the space occupying lesions (SOL) developed. However, the involvement of Trypanosoma cruzi is also described but appears to be less frequent in acquired immunodeficiency syndrome (AIDS) and transplant recipients, associated with necrotizing myocarditis and neurological symptoms related to the occurrence of necrotizing pseudotumoral encephalitis (NPE) and meningoencephalitis (NME). The present work aims to present a Venezuelan case of NME associated with the coinfection of HIV and a T. cruzi-like trypanosomatid as well as its evolution and diagnosis by histopathological techniques, electron microscopy, and PCR methods using formalin-fixed- (FF-) and paraffin-embedded- (PE-) tissues. Postmortem cytological studies of leptomeninges imprints reveal the presence of trypomastigotes of Trypanosoma sp. Histopathological and electron microscopy studies allowed us to identify an amastigote stage and to reject the involvement of other opportunistic microorganisms as the etiological agent of the SOL. The definitive confirmation of T. cruzi as the etiological agent was achieved by PCR suggesting that the NME by T. cruzi was due to a reactivation of Chagas' disease. PMID:25763312

Risks and Benefits of Rapid Clozapine Titration.

PubMed

Lochhead, Jeannie D; Nelson, Michele A; Schneider, Alan L

2016-05-18

Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

Morphologic Features of the Recipient Heart in Patients Having Cardiac Transplantation and Analysis of the Congruence or Incongruence Between the Clinical and Morphologic Diagnoses

PubMed Central

Roberts, William C.; Roberts, Carey Camille; Ko, Jong Mi; Filardo, Giovanni; Capehart, John Edward; Hall, Shelley Anne

2014-01-01

Abstract Cardiac transplantation (CT) has been one of the great medical advances of the last nearly 50 years. We studied the explanted hearts of 314 patients having CT at Baylor University Medical Center Dallas from 1993 to 2012, and compared the morphologic diagnoses to the clinical diagnoses before CT. Among the 314 patients the morphologic and clinical diagnoses were congruent in 272 (87%) and incongruent in 42 (13%). Most of the incongruity occurred among the 166 patients with non-ischemic cardiomyopathy (non-IC) (36/166 [22%]), and of that group the major incongruity occurred among the patients with hypertrophic cardiomyopathy (7/17 [41%]), non-compaction left ventricular cardiomyopathy (NCLVC) (3/3 [100%]), mononuclear myocarditis (3/3 [100%]), arrhythmogenic right ventricular cardiomyopathy (ARVC) (4/4 [100%]), and cardiac sarcoidosis (8/8 [100%]). The phrase “non-IC” is a general term that includes several subsets of cardiac diseases and simply means “insignificant narrowing of 1 or more of the epicardial coronary arteries,” but it does not specify the specific cause of the heart failure leading to CT. A number of cardiac illustrations are provided to demonstrate the morphologic variability occurring among the patients with IC and non-IC. PMID:25181314

Single nucleotide polymorphisms in the bovine Histophilus somni genome; a comparison of new and old isolates.

PubMed

Madampage, Claudia Avis; Rawlyk, Neil; Crockford, Gordon; Van Donkersgoed, Joyce; Dorin, Craig; Potter, Andrew

2015-07-01

Histophilus somni, a causative agent of the bovine respiratory disease complex, can also cause a variety of systemic disorders, including bronchopneumonia, myocarditis, pericarditis, arthritis, pleuritis, and infectious thrombotic meningoencephalitis. The purpose of this study was to determine if currently circulating strains differ from those of the 1980s by identifying genomic changes. Single nucleotide polymorphisms (SNPs) and insertion and deletion (INDEL) sites were examined by whole-genome sequencing in 12 samples, 6 old and 6 new. The 31 028 SNP/INDELs recorded were compared against the reference genome sequence of the pathogenic H. somni strain 2336. The distribution of about 75% of these SNPs within a specified gene differed between old and new isolates and did not follow any particular pattern. The other 25% clustered into 2 groups containing the same SNPs in various genes: group I included 5 old isolates and 1 new isolate; group II included 5 new isolates and 1 old isolate. For putative virulence genes there were more SNPs in group I compared with strain 2336, itself an older isolate, than in group II. Although only 25% of all the SNPs formed 2 clusters, the results suggest some genetic difference in various genes between old and new strains.

Single nucleotide polymorphisms in the bovine Histophilus somni genome; a comparison of new and old isolates

PubMed Central

Madampage, Claudia Avis; Rawlyk, Neil; Crockford, Gordon; Van Donkersgoed, Joyce; Dorin, Craig; Potter, Andrew

2015-01-01

Histophilus somni, a causative agent of the bovine respiratory disease complex, can also cause a variety of systemic disorders, including bronchopneumonia, myocarditis, pericarditis, arthritis, pleuritis, and infectious thrombotic meningoencephalitis. The purpose of this study was to determine if currently circulating strains differ from those of the 1980s by identifying genomic changes. Single nucleotide polymorphisms (SNPs) and insertion and deletion (INDEL) sites were examined by whole-genome sequencing in 12 samples, 6 old and 6 new. The 31 028 SNP/INDELs recorded were compared against the reference genome sequence of the pathogenic H. somni strain 2336. The distribution of about 75% of these SNPs within a specified gene differed between old and new isolates and did not follow any particular pattern. The other 25% clustered into 2 groups containing the same SNPs in various genes: group I included 5 old isolates and 1 new isolate; group II included 5 new isolates and 1 old isolate. For putative virulence genes there were more SNPs in group I compared with strain 2336, itself an older isolate, than in group II. Although only 25% of all the SNPs formed 2 clusters, the results suggest some genetic difference in various genes between old and new strains. PMID:26130851

Recent Progress in Understanding Coxsackievirus Replication, Dissemination, and Pathogenesis

PubMed Central

Sin, Jon; Mangale, Vrushali; Thienphrapa, Wdee; Gottlieb, Roberta A.; Feuer, Ralph

2015-01-01

Coxsackieviruses (CVs) are relatively common viruses associated with a number of serious human diseases, including myocarditis and meningo-encephalitis. These viruses are considered cytolytic yet can persist for extended periods of time within certain host tissues requiring evasion from the host immune response and a greatly reduced rate of replication. A member of Picornaviridae family, CVs have been historically considered non-enveloped viruses – although recent evidence suggest that CV and other picornaviruses hijack host membranes and acquire an envelope. Acquisition of an envelope might provide distinct benefits to CV virions, such as resistance to neutralizing antibodies and efficient nonlytic viral spread. CV exhibits a unique tropism for progenitor cells in the host which may help to explain the susceptibility of the young host to infection and the establishment of chronic disease in adults. CVs have also been shown to exploit autophagy to maximize viral replication and assist in unconventional release from target cells. In this article, we review recent progress in clarifying virus replication and dissemination within the host cell, identifying determinants of tropism, and defining strategies utilized by the virus to evade the host immune response. Also, we will highlight unanswered questions and provide future perspectives regarding the potential mechanisms of CV pathogenesis. PMID:26142496

Recurrent symptomatic ischemic stroke in a 46-year-old African male revealing Angio-Behçet with severe cardiovascular involvement.

PubMed

Marie, Ba Djibril; Aminata, Diack; Cherif, Mboup Mouhamed; Daouda, Fall Moussa

2017-03-01

Behçet'sdisease (BD) is a chronic, multisystem vasculitis. It is categorized under variable vessel vasculitis in the new Chapel Hill nomenclature as it involves blood vessels of any type and size. It is characterized by relapsing aphthous ulcers commonly occurring in the oral mucosa and genitalia with ocular involvement. Other organ systems may be involved any time throughout the course of the disease. The exact cause is unknown. However, combination of genetic and environmental factors is likely to play a role. Cardiac involvement may occur in the form of intracardiac thrombus, endocarditis, myocarditis, pericarditis, endomyocardial fibrosis, coronary arteritis, myocardial infarction, and valvular disease. We present a case of Angio-Behçet in a 46-year-old African male with severe cardiovascular involvement including pulmonary artery hypertension (PAH), right ventricular failure and left ventricular diastolic dysfunction diagnosed after 2 episodes of symptomatic ischemic stroke resulting from complete occlusion of the right internal carotid artery (ICA) up to its intracranial portion. Immunosuppressive and anticoagulant therapies have induced improvement in cardiac manifestations. Nevertheless, prompt recognition of the primarily vascular manifestation of BD without mucocutaneous manifestations was responsible for considerable delay that did not afford surgical therapy for the carotid occlusion.

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine.

PubMed

De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

2018-05-01

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

Pulmonary and central nervous system pathology in fatal cases of hand foot and mouth disease caused by enterovirus A71 infection.

PubMed

Wang, Zijun; Nicholls, John M; Liu, Fengfeng; Wang, Joshua; Feng, Zijian; Liu, Dongge; Sun, Yanni; Zhou, Cheng; Li, Yunqian; Li, Hai; Qi, Shunxiang; Huang, Xueyong; Sui, Jilin; Liao, Qiaohong; Peiris, Malik; Yu, Hongjie; Wang, Yu

2016-04-01

In the past 17 years, neurological disease associated with enterovirus A71 (EV-A71) has increased dramatically in the Asia-Pacific region with a high fatality rate in young infants, often due to pulmonary oedema, however the mechanism of this oedema remains obscure. We analysed the brainstem, heart and lungs of 15 fatal cases of confirmed EV-A71 infection in order to understand the pathophysiological mechanism of death and pulmonary oedema. In keeping with other case studies, the main cause of death was neurogenic pulmonary oedema. In the brainstem, 11 cases showed inflammation and all cases showed parenchymal inflammation with seven cases showing moderate or severe clasmatodendrosis. No viral antigen was detected in sections of the brainstem in any of the cases. All fatal cases showed evidence of pulmonary oedema; however, there was absence of direct pulmonary viral damage or myocarditis-induced damage and EV-A71 viral antigen staining was negative. Though there was no increase in staining for Na/K-ATPase, 11 of the 15 cases showed a marked reduction in aquaporin-4 staining in the lung, and this reduction may contribute to the development of fatal pulmonary oedema. Copyright © 2016. Published by Elsevier B.V.

Molecular testing of adult Pacific salmon and trout (Oncorhynchus spp.) for several RNA viruses demonstrates widespread distribution of piscine orthoreovirus in Alaska and Washington

USGS Publications Warehouse

Purcell, Maureen; Thompson, Rachel L.; Evered, Joy; Kerwin, John; Meyers, Ted R.; Stewart, Bruce; Winton, James

2018-01-01

This research was initiated in conjunction with a systematic, multiagency surveillance effort in the United States (U.S.) in response to reported findings of infectious salmon anaemia virus (ISAV) RNA in British Columbia, Canada. In the systematic surveillance study reported in a companion paper, tissues from various salmonids taken from Washington and Alaska were surveyed for ISAV RNA using the U.S.-approved diagnostic method, and samples were released for use in this present study only after testing negative. Here, we tested a subset of these samples for ISAV RNA with three additional published molecular assays, as well as for RNA from salmonid alphavirus (SAV), piscine myocarditis virus (PMCV) and piscine orthoreovirus (PRV). All samples (n = 2,252; 121 stock cohorts) tested negative for RNA from ISAV, PMCV, and SAV. In contrast, there were 25 stock cohorts from Washington and Alaska that had one or more individuals test positive for PRV RNA; prevalence within stocks varied and ranged from 2% to 73%. The overall prevalence of PRV RNA-positive individuals across the study was 3.4% (77 of 2,252 fish tested). Findings of PRV RNA were most common in coho (Oncorhynchus kisutch Walbaum) and Chinook (O. tshawytscha Walbaum) salmon.

Discovery of three novel coccidian parasites infecting California sea lions (Zalophus californianus), with evidence of sexual replication and interspecies pathogenicity.

PubMed

Colegrove, Kathleen M; Grigg, Michael E; Carlson-Bremer, Daphne; Miller, Robin H; Gulland, Frances M D; Ferguson, David J P; Rejmanek, Daniel; Barr, Bradd C; Nordhausen, Robert; Melli, Ann C; Conrad, Patricia A

2011-10-01

Enteric protozoal infection was identified in 5 stranded California sea lions (Zalophus californianus). Microscopically, the apical cytoplasm of distal jejunal enterocytes contained multiple stages of coccidian parasites, including schizonts with merozoites and spherical gametocytes, which were morphologically similar to coccidians. By histopathology, organisms appeared to be confined to the intestine and accompanied by only mild enteritis. Using electron microscopy, both sexual (microgametocytes, macrogamonts) and asexual (schizonts, merozoites) coccidian stages were identified in enterocytes within parasitophorous vacuoles, consistent with apicomplexan development in a definitive host. Serology was negative for tissue cyst-forming coccidians, and immunohistochemistry for Toxoplasma gondii was inconclusive and negative for Neospora caninum and Sarcocystis neurona. Analysis of ITS-1 gene sequences amplified from frozen or formalin-fixed paraffin-embedded intestinal sections identified DNA sequences with closest homology to Neospora sp. (80%); these novel sequences were referred to as belonging to coccidian parasites "A," "B," and "C." Subsequent molecular analyses completed on a neonatal harbor seal (Phoca vitulina) with protozoal lymphadenitis, hepatitis, myocarditis, and encephalitis showed that it was infected with a coccidian parasite bearing the "C" sequence type. Our results indicate that sea lions likely serve as definitive hosts for 3 newly described coccidian parasites, at least 1 of which is pathogenic in a marine mammal intermediate host species.

Pacemaker lead perforation of the right ventricle associated with Moraxella phenylpyruvica infection in a dog.

PubMed

Ciavarella, A; Nimmo, J; Hambrook, L

2016-04-01

A 13-year-old neutered male Border Collie was presented with acute onset syncope, weakness and anorexia 10 months after transvenous pacemaker implantation. The patient was laterally recumbent, bradycardic (36 beats/min) and febrile (40.7°C) on presentation. An electrocardiogram (ECG) revealed recurrence of third-degree atrioventricular block with a ventricular escape rhythm. Fluoroscopy identified migration of the pacemaker tip through the apex of the right ventricle. Echocardiography failed to reveal any evidence of pericardial effusion or cardiac tamponade. Full postmortem was performed after euthanasia. The pacemaker lead had perforated the apex of the right ventricle and lodged in the right pleural space. Culture of blood (taken antemortem), pericardial sac, right ventricular wall (surrounding pacemaker lead), pacemaker lead tip and pericardial fluid revealed a pure growth of Moraxella phenylpyruvica. Bacteraemia associated with M. phenylpyruvica has never been reported in the dog, but sporadic cases are reported in humans. Infection could have resulted from either pre-existing myocarditis or opportunistic infection and bacteraemia post pacemaker implantation. Evaluation of the pacemaker function at regular intervals would allow early detection of poor pacemaker-to-myocardium contact, which would prompt further investigation of pacemaker lead abnormalities such as perforation. © 2016 Australian Veterinary Association.

Characterization of myocardial lesions associated with cardiomyopathy syndrome in Atlantic salmon, Salmo salar L., using laser capture microdissection.

PubMed

Wiik-Nielsen, J; Løvoll, M; Fritsvold, C; Kristoffersen, A B; Haugland, Ø; Hordvik, I; Aamelfot, M; Jirillo, E; Koppang, E O; Grove, S

2012-12-01

Cardiomyopathy syndrome (CMS) in Atlantic salmon, Salmo salar L., is characterized by focal infiltration in the spongy myocardium and endocardium of the heart. The origin of the mononuclear infiltrate is unknown. Using experimentally infected fish, we investigated localization of the causative agent, piscine myocarditis virus (PMCV), within the heart and characterized the cell population associated with myocardial lesions. Cellular and transcriptional characteristics in the lesions were compared with adjacent non-infiltrated tissues using laser capture microdissection, RT-qPCR and immunohistochemistry. Our results reveal that PMCV is almost exclusively present in myocardial lesions. The inflammatory infiltrate comprises a variety of leucocyte populations, including T cells, B cells, MHC class II(+) and CD83(+) cells, most likely of the macrophage line. Correlation analyses demonstrated co-ordinated leucocyte activity at the site of the virus infection. Cellular proliferation and/or DNA repair was demonstrated within the myocardial lesions. Different cell populations, mainly myocytes, stained positive for proliferating cell nuclear antigen (PCNA). Densities of endothelial cells and fibroblasts were not significantly increased. The simultaneous presence of PMCV and various inflammatory cells in all myocardial lesions analysed may indicate that both viral lytic and immunopathological effects may contribute to the pathogenesis of CMS. © 2012 Blackwell Publishing Ltd.

Scrub Typhus: An Emerging Threat

PubMed Central

Chakraborty, Sayantani; Sarma, Nilendu

2017-01-01

Scrub typhus is caused by Orientia tsutsugamushi (formerly Rickettsia) and is transmitted to humans by an arthropod vector of the Trombiculidae family (Leptotrombidium deliense and L. akamushi). It is the most common re-emerging Rickettsial infection in India and many other South East Asian countries. In fact, scrub typhus is confined geographically to the Asia Pacific region, a billion people are at risk and nearly a million cases are reported every year. Scrub typhus appears particularly to be distributed in the tsutsugamushi triangle which is distributed over a very wide area of 13 million km2 bound by Japan in the east, through China, the Philippines, tropical Australia in the south, and west through India, Pakistan, possibly to Tibet to Afghanistan, and southern parts of the USSR in the north. Eschar is the characteristic lesion that starts as a vesicular lesion at the site of mite feeding. Later, an ulcer forms with black necrotic center and an erythematous border along with regional lymphadenopathy. Other features are fever, maculopapular rash starting from the trunk, and spreading to the limbs. It may affect the central nervous system, cardiovascular system, renal, respiratory, and gastrointestinal systems. Serious complication in the form of myocarditis, pneumonia, meningoencephalitis, acute renal failure, gastrointestinal bleeding, and even acute respiratory distress syndrome may develop. Tetracycline or chloramphenicol remains the main stay of therapy. PMID:28979009

Shaggy Lame Fox Syndrome in Pribilof Island Arctic Foxes ( Alopex lagopus pribilofensis), Alaska.

PubMed

Spraker, T R; White, P A

2017-03-01

A previously unrecognized condition is described in wild free-ranging Pribilof arctic foxes ( Alopex lagopus pribilofensis) from the Pribilof Islands, Alaska, USA. This condition is called shaggy lame fox syndrome (SLFS) denoting the primary clinical signs first observed. Criteria used to suspect SLFS on gross examination included emaciation, failure to shed winter pelage and moderate to severe polyarthritis. Criteria used to confirm SLFS histologically included polyarthritis (characterized by lymphoplasmacytic synovitis, tenosynovitis, bursitis, periosteal bony proliferation, and periarticular lymphoplasmacytic vasculitis) and systemic leukocytoclastic vasculitis. Other histological lesions often found included renal cortical infarcts, myocarditis with myocardial infarcts, lymphoplasmacytic meningitis, lymphoplasmacytic cuffing of meningeal and a few cerebral vessels, and cavitating infarcts of the brainstem and thalamus. The cause of SLFS is not known at this time; however, the gross and histological lesions suggest that the cause of SLFS may be a bacterial polyarthritis with a secondary immune-mediated vasculitis. These lesions are consistent with changes described with Erysipelothrix rhusiopathiae in domestic dogs; E. rhusiopathiae was identified from the synovial membrane of a swollen stifle joint and the kidney from one fox using real-time polymerase chain reaction and with culture from a fox that had gross and histological lesions of SLFS. Therefore, E. rhusiopathiae is a possible etiological agent for SLFS.

Induction of the 'ASIA' syndrome in NZB/NZWF1 mice after injection of complete Freund's adjuvant (CFA).

PubMed

Bassi, N; Luisetto, R; Del Prete, D; Ghirardello, A; Ceol, M; Rizzo, S; Iaccarino, L; Gatto, M; Valente, M L; Punzi, L; Doria, A

2012-02-01

Adjuvants, commonly used in vaccines, may be responsible for inducing autoimmunity and autoimmune diseases, both in humans and mice. The so-called 'ASIA' (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome has been recently described, which is caused by the exposure to a component reproducing the effect of adjuvants. The aim of our study was to evaluate the effect of injection of complete Freund's adjuvant (CFA) in NZB/NZWF1 mice, a lupus-prone murine model. We injected 10 NZB/NZWF1 mice with CFA/PBS and 10 with PBS, three times, 3 weeks apart, and followed-up until natural death. CFA-injected mice developed both anti-double-stranded DNA and proteinuria earlier and at higher levels than the control group. Proteinuria-free survival rate and survival rate were significantly lower in CFA-treated mice than in the control mice (p = 0.002 and p = 0.001, respectively). Histological analyses showed a more severe glomerulonephritis in CFA-injected mice compared with the control mice. In addition, lymphoid hyperplasia in spleen and lungs, myocarditis, and vasculitis were observed in the former, but not in the latter group. In conclusion, the injection of CFA in NZB/NZWF1 mice accelerated autoimmune manifestations resembling 'ASIA' syndrome in humans.

Distribution of late gadolinium enhancement in various types of cardiomyopathies: Significance in differential diagnosis, clinical features and prognosis

PubMed Central

Satoh, Hiroshi; Sano, Makoto; Suwa, Kenichiro; Saitoh, Takeji; Nobuhara, Mamoru; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Hayashi, Hideharu

2014-01-01

The recent development of cardiac magnetic resonance (CMR) techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution. We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies (ICM and NICM), especially in terms of the location and distribution of late gadolinium enhancement (LGE). CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory, and the subendocardial or transmural LGE. LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer. The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function, including dilated cardiomyopathy, end-stage hypertrophic cardiomyopathy (HCM), cardiac sarcoidosis, and myocarditis, and those with diffuse left ventricular (LV) hypertrophy including HCM, cardiac amyloidosis and Anderson-Fabry disease. A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy. In arrhythmogenic right ventricular cardiomyopathy/dysplasia, an enhancement of right ventricular (RV) wall with functional and morphological changes of RV becomes apparent. Finally, the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments. PMID:25068019

Infusion of solutions of pre-irradiated components in rats.

PubMed

Pappas, Georgina; Arnaud, Francoise; Haque, Ashraful; Kino, Tomoyuki; Facemire, Paul; Carroll, Erica; Auker, Charles; McCarron, Richard; Scultetus, Anke

2016-06-01

The objective of this study was to conduct a 14-day toxicology assessment for intravenous solutions prepared from irradiated resuscitation fluid components and sterile water. Healthy Sprague Dawley rats (7-10/group) were instrumented and randomized to receive one of the following Field IntraVenous Resuscitation (FIVR) or commercial fluids; Normal Saline (NS), Lactated Ringer's, 5% Dextrose in NS. Daily clinical observation, chemistry and hematology on days 1,7,14, and urinalysis on day 14 were evaluated for equivalence using a two sample t-test (p<0.05). A board-certified pathologist evaluated organ histopathology on day 14. Equivalence was established for all observation parameters, lactate, sodium, liver enzymes, creatinine, WBC and differential, and urinalysis values. Lack of equivalence for hemoglobin (p=0.055), pH (p=0.0955), glucose (p=0.0889), Alanine-Aminotransferase (p=0.1938), albumin (p=0.1311), and weight (p=0.0555, p=0.1896), was deemed not clinically relevant due to means within physiologically normal ranges. Common microscopic findings randomly distributed among animals of all groups were endocarditis/myocarditis and pulmonary lesions. These findings are consistent with complications due to long-term catheter use and suggest no clinically relevant differences in end-organ toxicity between animals infused with FIVR versus commercial fluids. Copyright © 2016 Elsevier GmbH. All rights reserved.

A role for extracellular amastigotes in the immunopathology of Chagas disease.

PubMed

Scharfstein, J; Morrot, A

1999-01-01

In spite of the growing knowledge obtained about immune control of Trypanosoma cruzi infection, the mechanisms responsible for the variable clinico-pathological expression of Chagas disease remain unknown. In a twist from previous concepts, recent studies indicated that tissue parasitism is a pre-requisite for the development of chronic myocarditis. This fundamental concept, together with the realization that T. cruzi organisms consist of genetically heterogeneous clones, offers a new framework for studies of molecular pathogenesis. In the present article, we will discuss in general terms the possible implications of genetic variability of T. cruzi antigens and proteases to immunopathology. Peptide epitopes from a highly polymorphic subfamily of trans-sialidase (TS) antigens were recently identified as targets of killer T cell (CTL) responses, both in mice and humans. While some class I MHC restricted CTL recognize epitopes derived from amastigote-specific TS-related antigens (TSRA), others are targeted to peptide epitopes originating from trypomastigote-specific TSRA. A mechanistic hypothesis is proposed to explain how the functional activity and specificity of class I MHC restricted killer T cells may control the extent to which tissue are exposed to prematurely released amastigotes. Chronic immunopathology may be exacerbated due the progressive accumulation of amastigote-derived antigens and pro-inflammatory molecules (eg. GPI-mucins and kinin-releasing proteases) in dead macrophage bodies.

Prevalence of Chagas Disease among Solid Organ-Transplanted Patients in a Nonendemic Country.

PubMed

Salvador, Fernando; Sánchez-Montalvá, Adrián; Sulleiro, Elena; Moreso, Francesc; Berastegui, Cristina; Caralt, Mireia; Pinazo, María-Jesús; Moure, Zaira; Los-Arcos, Ibai; Len, Oscar; Gavaldà, Joan; Molina, Israel

2018-03-01

Reactivation of Chagas disease in the chronic phase may occur after solid organ transplantation, which may result in high parasitemia and severe clinical manifestations such as myocarditis and meningoencephalitis. The aim of the present study is to describe the prevalence of Chagas disease among solid organ-transplanted patients in a tertiary hospital from a nonendemic country. A cross-sectional study was performed at Vall d'Hebron University Hospital (Barcelona, Spain) from April to September 2016. Chagas disease screening was performed through serological tests in adult patients coming from endemic areas that had received solid organ transplantation and were being controlled in our hospital during the study period. Overall, 42 patients were included, 20 (47.6%) were male and median age was 50.5 (23-73) years. Transplanted organs were as follows: 18 kidneys, 17 lungs, and 7 livers. Three patients had Chagas disease, corresponding to a prevalence among this group of solid organ-transplanted patients of 7.1%. All three patients were born in Bolivia, had been diagnosed with Chagas disease and received specific treatment before the organ transplantation. We highly recommend providing screening tests for Chagas disease in patients with or candidates for solid organ transplantation coming from endemic areas, early treatment with benznidazole, and close follow-up to prevent clinical reactivations.

Anti-voltage-gated potassium channel Kv1.4 antibodies in myasthenia gravis.

PubMed

Romi, Fredrik; Suzuki, Shigeaki; Suzuki, Norihiro; Petzold, Axel; Plant, Gordon T; Gilhus, Nils Erik

2012-07-01

Myasthenia gravis (MG) is an autoimmune disease characterized by skeletal muscle weakness mainly caused by acetylcholine receptor antibodies. MG can be divided into generalized and ocular, and into early-onset (<50 years of age) and late-onset (≥50 years of age). Anti-Kv1.4 antibodies targeting α-subunits (Kv1.4) of the voltage-gated potassium K(+) channel occurs frequently among patients with severe MG, accounting for 18% of a Japanese MG population. The aim of this study was to characterize the clinical features and serological associations of anti-Kv1.4 antibodies in a Caucasian MG population with mild and localized MG. Serum samples from 129 Caucasian MG patients with mainly ocular symptoms were tested for the presence of anti-Kv1.4 antibodies and compared to clinical and serological parameters. There were 22 (17%) anti-Kv1.4 antibody-positive patients, most of them women with late-onset MG, and all of them with mild MG. This contrasts to the Japanese anti-Kv1.4 antibody-positive patients who suffered from severe MG with bulbar symptoms, myasthenic crisis, thymoma, myocarditis and prolonged QT time on electrocardiography, despite equal anti-Kv1.4 antibody occurrence in both populations. No other clinical or serological parameters influenced anti-Kv1.4 antibody occurrence.

Vaccination with Trypanosoma rangeli induces resistance of guinea pigs to virulent Trypanosoma cruzi.

PubMed

Basso, B; Moretti, E; Fretes, R

2014-01-15

Chagas' disease, endemic in Latin America, is spread in natural environments through animal reservoirs, including marsupials, mice and guinea pigs. Farms breeding guinea pigs for food are located in some Latin-American countries with consequent risk of digestive infection. The aim of this work was to study the effect of vaccination with Trypanosoma rangeli in guinea pigs challenged with Trypanosoma cruzi. Animals were vaccinated with fixated epimastigotes of T. rangeli, emulsified with saponin. Controls received only PBS. Before being challenged with T. cruzi, parasitemia, survival rates and histological studies were performed. The vaccinated guinea pigs revealed significantly lower parasitemia than controls (p<0.0001-0.01) and a discrete lymphomonocytic infiltrate in cardiac and skeletal muscles was present. In the chronic phase, the histological view was normal. In contrast, control group revealed amastigote nests and typical histopathological alterations compatible with chagasic myocarditis, endocarditis and pericarditis. These results, together with previous works in our laboratory, show that T. rangeli induces immunoprotection in three species of animals: mice, guinea pigs and dogs. The development of vaccines for use in animals, like domestic dogs and guinea pigs in captivity, opens up new opportunities for preventive tools, and could reduce the risk of infection with T. cruzi in the community. Copyright © 2013 Elsevier B.V. All rights reserved.

The Impact of Juvenile Coxsackievirus Infection on Cardiac Progenitor Cells and Postnatal Heart Development

PubMed Central

Sin, Jon; Puccini, Jenna M.; Huang, Chengqun; Konstandin, Mathias H.; Gilbert, Paul E.; Sussman, Mark A.; Gottlieb, Roberta A.; Feuer, Ralph

2014-01-01

Coxsackievirus B (CVB) is an enterovirus that most commonly causes a self-limited febrile illness in infants, but cases of severe infection can manifest in acute myocarditis. Chronic consequences of mild CVB infection are unknown, though there is an epidemiologic association between early subclinical infections and late heart failure, raising the possibility of subtle damage leading to late-onset dysfunction, or chronic ongoing injury due to inflammatory reactions during latent infection. Here we describe a mouse model of juvenile infection with a subclinical dose of coxsackievirus B3 (CVB3) which showed no evident symptoms, either immediately following infection or in adult mice. However following physiological or pharmacologically-induced cardiac stress, juvenile-infected adult mice underwent cardiac hypertrophy and dilation indicative of progression to heart failure. Evaluation of the vasculature in the hearts of adult mice subjected to cardiac stress showed a compensatory increase in CD31+ blood vessel formation, although this effect was suppressed in juvenile-infected mice. Moreover, CVB3 efficiently infected juvenile c-kit+ cells, and cardiac progenitor cell numbers were reduced in the hearts of juvenile-infected adult mice. These results suggest that the exhausted cardiac progenitor cell pool following juvenile CVB3 infection may impair the heart's ability to increase capillary density to adapt to increased load. PMID:25079373

Pathology of Chronic Chagas Cardiomyopathy in the United States:  A Detailed Review of 13 Cardiectomy Cases.

PubMed

Kransdorf, Evan P; Fishbein, Mike C; Czer, Lawrence S C; Patel, Jignesh K; Velleca, Angela; Tazelaar, Henry D; Roy, R Raina; Steidley, D Eric; Kobashigawa, Jon A; Luthringer, Daniel J

2016-08-01

The pathologic features of chronic Chagas cardiomyopathy may not be widely appreciated in the United States. We sought to describe the gross, microscopic, immunohistochemical, and molecular pathology features useful to diagnose chronic Chagas cardiomyopathy. The features from a case series of cardiectomy specimens of patients undergoing heart transplantation (12 patients) or mechanical circulatory support device implantation (one patient) for chronic Chagas cardiomyopathy at three institutions in the United States are reported and analyzed. Gross findings included enlarged and dilated ventricles (100% of cases), mural thrombi (54%), epicardial plaques (42%), and left ventricular aneurysm (36%). Microscopic evaluation revealed myocarditis (100% of cases) characterized by mononuclear cell infiltration, fibrosis (100%), nonnecrotizing granulomas (62%), and giant cells (38%). Two specimens (15%) showed rare intracellular amastigotes. Immunohistochemical assays for Trypanosoma cruzi organisms were negative in all cardiectomy specimens, whereas tissue polymerase chain reaction was positive in six (54%) of 11 cases. The gross and microscopic features of chronic Chagas cardiomyopathy in the United States appear similar to those reported in endemic countries. Importantly, tissue polymerase chain reaction may be useful to confirm the diagnosis. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cardiomyopathy syndrome in Atlantic salmon Salmo salar L.: A review of the current state of knowledge.

PubMed

Garseth, Å H; Fritsvold, C; Svendsen, J C; Bang Jensen, B; Mikalsen, A B

2018-01-01

Cardiomyopathy syndrome (CMS) is a severe cardiac disease affecting Atlantic salmon Salmo salar L. The disease was first recognized in farmed Atlantic salmon in Norway in 1985 and subsequently in farmed salmon in the Faroe Islands, Scotland and Ireland. CMS has also been described in wild Atlantic salmon in Norway. The demonstration of CMS as a transmissible disease in 2009, and the subsequent detection and initial characterization of piscine myocarditis virus (PMCV) in 2010 and 2011 were significant discoveries that gave new impetus to the CMS research. In Norway, CMS usually causes mortality in large salmon in ongrowing and broodfish farms, resulting in reduced fish welfare, significant management-related challenges and substantial economic losses. The disease thus has a significant impact on the Atlantic salmon farming industry. There is a need to gain further basic knowledge about the virus, the disease and its epidemiology, but also applied knowledge from the industry to enable the generation and implementation of effective prevention and control measures. This review summarizes the currently available, scientific information on CMS and PMCV with special focus on epidemiology and factors influencing the development of CMS. © 2017 The Authors. Journal of Fish Diseases Published by John Wiley & Sons Ltd.

Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy.

PubMed

Watanabe, Kenichi; Sreedhar, Remya; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Giridharan, Vijayasree V; Antony, Shanish; Harima, Meilei; Nakamura, Masahiko; Suzuki, Kenji; Suzuki, Hiroshi; Sone, Hirohito; Arumugam, Somasundaram

2017-03-01

Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Acute Physiological Responses to Short- and Long-Stage High-Intensity Interval Exercise in Cardiac Rehabilitation: A Pilot Study

PubMed Central

Tschakert, Gerhard; Kroepfl, Julia M.; Mueller, Alexander; Harpf, Hanns; Harpf, Leonhard; Traninger, Heimo; Wallner-Liebmann, Sandra; Stojakovic, Tatjana; Scharnagl, Hubert; Meinitzer, Andreas; Pichlhoefer, Patriz; Hofmann, Peter

2016-01-01

Despite described benefits of aerobic high-intensity interval exercise (HIIE), the acute responses during different HIIE modes and associated health risks have only been sparsely discovered in heart disease patients. Therefore, the aim of this study was to investigate the acute responses for physiological parameters, cardiovascular and inflammatory biomarkers, and catecholamines yielded by two different aerobic HIIE protocols compared to continuous exercise (CE) in phase III cardiac rehabilitation. Eight cardiac patients (7 with coronary heart disease, 1 with myocarditis; 7 males, 1 female; age: 63.0 ± 9.4 years; height: 1.74 ± 0.05 m; weight: 83.6 ± 8.7 kg), all but one treated with ß-blocking agents, performed a maximal symptom-limited incremental exercise test (IET) and three different exercise tests matched for mean load (Pmean) and total duration: 1) short HIIE with a peak workload duration (tpeak) of 20 s and a peak workload (Ppeak) equal to the maximum power output (Pmax) from IET; 2) long HIIE with a tpeak of 4 min, Ppeak was corresponding to the power output at 85 % of maximal heart rate (HRmax) from IET; 3) CE with a target workload equal to Pmean of both HIIE modes. Acute metabolic and peak cardiorespiratory responses were significantly higher during long HIIE compared to short HIIE and CE (p < 0.05) except HRpeak which tended to be higher in long HIIE than in short HIIE (p = 0.08). Between short HIIE and CE, no significant difference was found for any parameter. Acute responses of cardiovascular and inflammatory biomarkers and catecholamines didn’t show any significant difference between tests (p > 0.05). All health-related variables remained in a normal range in any test except NT-proBNP, which was already elevated at baseline. Despite a high Ppeak particularly in short HIIE, both HIIE modes were as safe and as well tolerated as moderate CE in cardiac patients by using our methodological approach. Key points High-intensity interval exercise (HIIE) with short peak workload durations (tpeak) induce a lower acute metabolic and peak cardiorespiratory response compared to intervals with long tpeak despite higher peak workload intensities and identical mean load. No significant difference for any physiological parameter was found between short HIIE and CE. Between short HIIE, long HIIE, and CE, no significant difference was found in the increase (or decrease, respectively,) of health related markers such as cardiovascular biomarkers, catecholamines, or inflammatory parameters during exercise. During all exercise modes, all risk markers remained in a normal range except for NT-proBNP which was, however, already elevated at baseline. Short HIIE, long HIIE, and CE were safely performed by patients with CHD or myocarditis in cardiac rehabilitation by using our methodological approach to exercise prescription. This approach included the prescription of exercise intensities with respect to LTP1, LTP2, and Pmax as well as a conscious setting of Pmean at a moderate level (80 % of PLTP2). Importantly, all exercise modes were matched for Pmean and exercise duration in order to enable a comparison of the three protocols. PMID:26957930

All-transretinoic acid (ATRA) treatment-related pancarditis and severe pulmonary edema in a child with acute promyelocytic leukemia.

PubMed

Işık, Pamir; Çetin, Ilker; Tavil, Betul; Azik, Fatih; Kara, Abdurrahman; Yarali, Nese; Tunc, Bahattin

2010-11-01

Use of all-transretinoic acid (ATRA) with other chemotherapeutic agents in the treatment of acute promyelocytic leukemia (APL) has been shown to cause the differentiation of abnormally granulated specific blast cells into mature granulocytes by acting on the t(15; 17) fusion gene product. The complete remission rate is increased and survival time is prolonged in APL patients who receive chemotherapy plus ATRA, whereas ATRA syndrome and other ATRA-related adverse effects including pseudo tumor cerebri, headache, severe bone pain, mucosal and skin dryness, hypercholesterolemia, and cheilitis may be observed especially during induction phase of the treatment. In this paper, we report a 9-year-old girl with APL who developed pancarditis while receiving the APL-93 treatment protocol. In our patient, endocarditis and myocarditis were initially determined after ATRA treatment during the induction part of the protocol. All findings disappeared after ATRA was discontinued. When ATRA was readministered in the maintenance part of the treatment protocol, she developed pancarditis and severe pulmonary edema. As her symptoms decreased dramatically with the discontinuation of ATRA and the initiation of steroid treatment, the clinical picture strongly suggested the ATRA treatment as the causative factor. To the best of our knowledge, this clinical picture of pancarditis secondary to ATRA treatment has not been reported earlier in the English literature.

Experience of a patient with an extracorporeal ventricular assist system who participated in a sleepover program.

PubMed

Gon, Shigeyoshi; Suematsu, Yoshihito; Morizumi, Sei; Shimizu, Tsuyoshi

2011-09-01

A 19-year-old woman suffered fulminant myocarditis owing to a mycoplasma infection and was inserted with an intra-aortic balloon pump and a percutaneous cardiopulmonary support. Antibiotics and gamma globulin were administered, however, the patient's cardiac function did not recover, and the TOYOBO ventricular assist device (VAD) was implanted. She had rehabilitation training such as maintaining a standing position at the bedside and walking in the hospital, and a hospital outing program to a family restaurant was conducted two times with the VAD. The patient wished to attend the coming-of-age ceremony in Tachikawa city, which is 3 h away from our hospital by car. Therefore, we planned the program including a night stay at her home. The patient and her family fully understood the risks and wished to participate in the sleepover program. In preparing for the sleepover, the patient and her family learned to operate the VAD, and she was able to move to the lavatory and through the house with the help of only her family. A physician and a clinical engineer stayed at her house for infusion of antibiotics and management of sudden changes. There was no adverse event. In Japan, the community support of patients with VAD is not yet established, and we hope that our experience becomes a help to support return to society for patients with VAD.

Interleukin 1 and Tumor Necrosis Factor Inhibit Cardiac Myocyte β -adrenergic Responsiveness

NASA Astrophysics Data System (ADS)

Gulick, Tod; Chung, Mina K.; Pieper, Stephen J.; Lange, Louis G.; Schreiner, George F.

1989-09-01

Reversible congestive heart failure can accompany cardiac allograft rejection and inflammatory myocarditis, conditions associated with an immune cell infiltrate of the myocardium. To determine whether immune cell secretory products alter cardiac muscle metabolism without cytotoxicity, we cultured cardiac myocytes in the presence of culture supernatants from activated immune cells. We observed that these culture supernatants inhibit β -adrenergic agonist-mediated increases in cultured cardiac myocyte contractility and intracellular cAMP accumulation. The myocyte contractile response to increased extracellular Ca2+ concentration is unaltered by prior exposure to these culture supernatants, as is the increase in myocyte intracellular cAMP concentration in response to stimulation with forskolin, a direct adenyl cyclase activator. Inhibition occurs in the absence of alteration in β -adrenergic receptor density or ligand binding affinity. Suppressive activity is attributable to the macrophage-derived cytokines interleukin 1 and tumor necrosis factor. Thus, these observations describe a role for defined cytokines in regulating the hormonal responsiveness and function of contractile cells. The effects of interleukin 1 and tumor necrosis factor on intracellular cAMP accumulation may be a model for immune modulation of other cellular functions dependent upon cyclic nucleotide metabolism. The uncoupling of agonist-occupied receptors from adenyl cyclase suggests that β -receptor or guanine nucleotide binding protein function is altered by the direct or indirect action of cytokines on cardiac muscle cells.

Recommendations for participation in competitive sport and leisure-time physical activity in individuals with cardiomyopathies, myocarditis and pericarditis.

PubMed

Pelliccia, Antonio; Corrado, Domenico; Bjørnstad, Hans Halvor; Panhuyzen-Goedkoop, Nicole; Urhausen, Axel; Carre, Francois; Anastasakis, Aris; Vanhees, Luc; Arbustini, Eloisa; Priori, Silvia

2006-12-01

Several relatively uncommon, but important cardiovascular diseases are associated with increased risk for acute cardiac events during exercise (including sudden death), such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and myo-pericarditis. Practising cardiologists are frequently asked to advise on exercise programmes and sport participation in young individuals with these cardiovascular diseases. Indeed, many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to a physically active lifestyle to take advantage of the many documented benefits of exercise. While recommendations dictating the participation in competitive sport for athletes with cardiomyopathies and myo-pericarditis have recently been published as a consensus document of the European Society of Cardiology, no European guidelines have addressed the possible participation of patients with cardiomyopathies in recreational and amateur sport activities. The present document is intended to offer a comprehensive overview to practising cardiologists and sport physicians of the recommendations governing safe participation in different types of competitive sport, as well as the participation in a variety of recreational physical activities and amateur sports in individuals with cardiomyopathies and myo-pericarditis. These recommendations, based largely on the experience and insights of the expert panel appointed by the European Society of Cardiology, include the most up-to-date information concerning regular exercise and sports activity in patients with cardiomyopathies and myo-pericarditis.

Rapid Clozapine Titration in Patients with Treatment Refractory Schizophrenia.

PubMed

Poyraz, Cana Aksoy; Özdemir, Armağan; Sağlam, Nazife Gamze Usta; Turan, Şenol; Poyraz, Burç Çağrı; Tomruk, Nesrin; Duran, Alaattin

2016-06-01

The aim of this study is to evaluate the safety and effectiveness of rapid clozapine titration in patients with schizophrenia in hospital settings. We conducted a retrospective two-center cohort study to compare the safety and effectiveness of clozapine with different titration rates in treatment-refractory patients with schizophrenia. In the first center, clozapine was started at 25-50 mg followed by 50-100 mg as needed every 6 h on day 1, followed by increases of 50-100 mg/day. In the second center, titration was slower; clozapine initiated with 12.5-50 mg on day 1 followed by increases of 25-50 mg/day. The number of days between starting of clozapine until discharge was shorter in the rapid titration group (22.4 ± 8.72 vs 27.0 ± 10.5, p = 0.1). Number of days of total hospital stay were significantly shorter in the rapid titration group (29.6 ± 10.6 vs 41.2 ± 14.8, p = 0.002). Hypotension was more common in the rapid titration group and one patient had suspected myocarditis. Rapid clozapine titration appeared safe and effective. The length of stay following initiation of clozapine was shorter in the rapid-titration group, although this was not statistically significant. However starting clozapine earlier together with rapid titration has significantly shortened the length of hospital stay in patients with treatment refractory schizophrenia.

Diseases and pathogens associated with mortality in Ontario beef feedlots.

PubMed

Gagea, Mihai I; Bateman, Kenneth G; van Dreumel, Tony; McEwen, Beverly J; Carman, Susy; Archambault, Marie; Shanahan, Rachel A; Caswell, Jeff L

2006-01-01

This study determined the prevalence of diseases and pathogens associated with mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or were euthanized within 60 days after arrival. Routine pathologic and microbiologic investigations, as well as immunohistochemical staining for detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99 calves that died or were euthanized within 60 days after arrival. Major disease conditions identified included fibrinosuppurative bronchopneumonia (49%), caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%). Viral infections identified were BVDV (35%), bovine respiratory syncytial virus (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%), Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes (19%). Pneumonia was the most frequent cause of mortality of beef calves during the first 2 months after arrival in feedlots, representing 69% of total deaths. The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar to that of fibrinosuppurative bronchopneumonia, and together, these diseases were the most common causes of pneumonia and death. M. bovis pneumonia and polyarthritis has emerged as an important cause of mortality in Ontario beef feedlots.

Targeted delivery of anti-coxsackievirus siRNAs using ligand-conjugated packaging RNAs.

PubMed

Zhang, Huifang M; Su, Yue; Guo, Songchuan; Yuan, Ji; Lim, Travis; Liu, Jing; Guo, Peixuan; Yang, Decheng

2009-09-01

Coxsackievirus B3 (CVB3) is a common pathogen of myocarditis. We previously synthesized a siRNA targeting the CVB3 protease 2A (siRNA/2A) gene and achieved reduction of CVB3 replication by 92% in vitro. However, like other drugs under development, CVB3 siRNA faces a major challenge of targeted delivery. In this study, we investigated a novel approach to deliver CVB3 siRNAs to a specific cell population (e.g. HeLa cells containing folate receptor) using receptor ligand (folate)-linked packaging RNA (pRNA) from bacterial phage phi29. pRNA monomers can spontaneously form dimers and multimers under optimal conditions by base-pairing between their stem loops. By covalently linking a fluorescence-tag to folate, we delivered the conjugate specifically to HeLa cells without the need of transfection. We further demonstrated that pRNA covalently conjugated to siRNA/2A achieved an equivalent antiviral effect to that of the siRNA/2A alone. Finally, the drug targeted delivery was further evaluated by using pRNA monomers or dimers, which carried both the siRNA/2A and folate ligand and demonstrated that both of them strongly inhibited CVB3 replication. These data indicate that pRNA as a siRNA carrier can specifically deliver the drug to target cells via its ligand and specific receptor interaction and inhibit virus replication effectively.

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

PubMed Central

De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

2018-01-01

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon. PMID:29796248

Mechanical Circulatory Support of the Critically Ill Child Awaiting Heart Transplantation

PubMed Central

Gazit, Avihu Z; Gandhi, Sanjiv K; C Canter, Charles

2010-01-01

The majority of children awaiting heart transplantation require inotropic support, mechanical ventilation, and/or extracorporeal membrane oxygenation (ECMO) support. Unfortunately, due to the limited pool of organs, many of these children do not survive to transplant. Mechanical circulatory support of the failing heart in pediatrics is a new and rapidly developing field world-wide. It is utilized in children with acute congestive heart failure associated with congenital heart disease, cardiomyopathy, and myocarditis, both as a bridge to transplantation and as a bridge to myocardial recovery. The current arsenal of mechanical assist devices available for children is limited to ECMO, intra-aortic balloon counterpulsation, centrifugal pump ventricular assist devices, the DeBakey ventricular assist device Child; the Thoratec ventricular assist device; and the Berlin Heart. In the spring of 2004, five contracts were awarded by the National Heart, Lung and Blood Institute to support preclinical development for a range of pediatric ventricular assist devices and similar circulatory support systems. The support of early development efforts provided by this program is expected to yield several devices that will be ready for clinical trials within the next few years. Our work reviews the current international experience with mechanical circulatory support in children and summarizes our own experience since 2005 with the Berlin Heart, comparing the indications for use, length of support, and outcome between these modalities. PMID:21286278

Case Report: Severe Imported Influenza Infections Developed during Travel in Reunion Island.

PubMed

Allyn, Jérôme; Brottet, Elise; Antok, Emmanuel; Dangers, Laurence; Persichini, Romain; Coolen-Allou, Nathalie; Roquebert, Bénédicte; Allou, Nicolas; Vandroux, David

2017-12-01

We report two cases of severe influenza infection imported by tourist patients from their country of origin and developed during travel. While studies have reported cases of influenza infections acquired during travel, here we examine two cases of severe influenza infection contracted in the country of origin that led to diagnosis and therapeutic problems in the destination country. No international recommendation exists concerning influenza vaccination before travel, and few countries recommend it for all travelers. Our study suggests that travel should be canceled when infectious signs are observed before departure. Influenza is a very common infection that is often benign, but sometimes very severe. The most severe cases include shock, acute respiratory distress syndrome (ARDS), myocarditis, rhabdomyolysis, and multiple organ failure. Management can require exceptional therapies, such as extracorporeal membrane oxygenation. A number of studies have focused on influenza infection in travelers. Cases of influenza acquired during travel have been reported in this literature, but no study has examined cases of influenza imported from the country of origin and developed while abroad. The latter situation may lead to 1) diagnostic problems during the nonepidemic season or in places where diagnostic techniques are lacking and 2) therapeutic difficulties resulting from the unavailability of techniques for the management of severe influenza infection in tourist areas. Here, we report two cases of extremely severe influenza infection imported by tourists from their country of origin and developed during travel.

Tricuspid and mitral regurgitation detected by color flow Doppler in the acute phase of Kawasaki disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, A.; Kamiya, T.; Tsuchiya, K.

Valvular lesions in the acute phase of Kawasaki disease were studied in 19 children. The patients were intensively observed by color flow Doppler every day from the day of hospitalization up to 12 days after the onset of the disease and 2 or more times a week thereafter, for up to 28 days. Mitral regurgitation (MR) was found in 9 patients (47%) and tricuspid regurgitation (TR) in 10 (53%). MRs were of transient type and confirmed from 7.5 +/- 1.6 (mean +/- standard deviation) to 13.1 +/- 6.5 days after the onset of the disease. Both types of valvular regurgitationmore » were mild. The direction of regurgitation was from the center of valvular coaptation toward the posterior wall of the atrium. Neither valvular prolapse nor valvular deformity was noted. In patients with MR, left ventricular ejection fraction on M-mode echocardiography was significantly lower in the acute phase than in the convalescent phase of the disease (p less than 0.05). Using gallium-67 scintigram, the positive uptake of the isotope was noted in 7 (88%) of 8 patients with MR, but not found at all in 8 patients free of MR. These results suggest that MR and TR are often transient in the acute phase of Kawasaki disease and could be attributed to myocarditis.« less

In Situ Detection of Autoreactive CD4 T Cells in Brain and Heart Using Major Histocompatibility Complex Class II Dextramers

PubMed Central

Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Jia, Ting; Elowsky, Christian; Li, Qingsheng; Zhou, You; Reddy, Jay

2014-01-01

This report demonstrates the use of major histocompatibility complex (MHC) class II dextramers for detection of autoreactive CD4 T cells in situ in myelin proteolipid protein (PLP) 139-151-induced experimental autoimmune encephalomyelitis (EAE) in SJL mice and cardiac myosin heavy chain-α (Myhc) 334-352-induced experimental autoimmune myocarditis (EAM) in A/J mice. Two sets of cocktails of dextramer reagents were used, where dextramers+ cells were analyzed by laser scanning confocal microscope (LSCM): EAE, IAs/PLP 139-151 dextramers (specific)/anti-CD4 and IAs/Theiler’s murine encephalomyelitis virus (TMEV) 70-86 dextramers (control)/anti-CD4; and EAM, IAk/Myhc 334-352 dextramers/anti-CD4 and IAk/bovine ribonuclease (RNase) 43-56 dextramers (control)/anti-CD4. LSCM analysis of brain sections obtained from EAE mice showed the presence of cells positive for CD4 and PLP 139-151 dextramers, but not TMEV 70-86 dextramers suggesting that the staining obtained with PLP 139-151 dextramers was specific. Likewise, heart sections prepared from EAM mice also revealed the presence of Myhc 334-352, but not RNase 43-56-dextramer+ cells as expected. Further, a comprehensive method has also been devised to quantitatively analyze the frequencies of antigen-specific CD4 T cells in the ‘Z’ serial images. PMID:25145797

Do Archaea and bacteria co-infection have a role in the pathogenesis of chronic chagasic cardiopathy?

PubMed

Higuchi, Maria de Lourdes; Kawakami, Joyce; Ikegami, Renata; Clementino, Maysa Beatriz Mandetta; Kawamoto, Flavio M; Reis, Marcia M; Bocchi, Edimar

2009-07-01

Chronic cardiopathy (CC) in Chagas disease is a fibrotic myocarditis with C5b-9 complement deposition. Mycoplasma and Chlamydia may interfere with the complement response. Proteolytic enzymes and archaeal genes that have been described in Trypanosoma cruzi may increase its virulence. Here we tested the hypothesis that different ratios of Mycoplasma, Chlamydia and archaeal organisms, which are frequent symbionts, may be associated with chagasic clinical forms. eight indeterminate form (IF) and 20 CC chagasic endomyocardial biopsies were submitted to in situ hybridization, electron and immunoelectron microscopy and PCR techniques for detection of Mycoplasma pneumoniae (MP), Chlamydia pneumoniae(CP), C5b-9 and archaeal-like bodies. MP and CP-DNA were always present at lower levels in CC than in IF (p < 0.001) and were correlated with each other only in CC. Electron microscopy revealed Mycoplasma, Chlamydia and two types of archaeal-like bodies. One had electron dense lipid content (EDL) and was mainly present in IF. The other had electron lucent content (ELC) and was mainly present in CC. In this group, ELC correlated negatively with the other microbes and EDL and positively with C5b-9. The CC group was positive for Archaea and T. cruzi DNA. In conclusion, different amounts of Mycoplasma, Chlamydia and archaeal organisms may be implicated in complement activation and may have a role in Chagas disease outcome.

Phenyl-alpha-tert-butyl nitrone reverses mitochondrial decay in acute Chagas' disease.

PubMed

Wen, Jian-Jun; Bhatia, Vandanajay; Popov, Vsevolod L; Garg, Nisha Jain

2006-12-01

In this study, we investigated the mechanism(s) of mitochondrial functional decline in acute Chagas' disease. Our data show a substantial decline in respiratory complex activities (39 to 58%) and ATP (38%) content in Trypanosoma cruzi-infected murine hearts compared with normal controls. These metabolic alterations were associated with an approximately fivefold increase in mitochondrial reactive oxygen species production rate, substantial oxidative insult of mitochondrial membranes and respiratory complex subunits, and >60% inhibition of mtDNA-encoded transcripts for respiratory complex subunits in infected myocardium. The antioxidant phenyl-alpha-tert-butyl nitrone (PBN) arrested the oxidative damage-mediated loss in mitochondrial membrane integrity, preserved redox potential-coupled mitochondrial gene expression, and improved respiratory complex activities (47 to 95% increase) and cardiac ATP level (>or=40% increase) in infected myocardium. Importantly, PBN resulted twofold decline in mitochondrial reactive oxygen species production rate in infected myocardium. Taken together, our data demonstrate the pathological significance of oxidative stress in metabolic decay and energy homeostasis in acute chagasic myocarditis and further suggest that oxidative injuries affecting mitochondrial integrity-dependent expression and activity of the respiratory complexes initiate a feedback cycle of electron transport chain inefficiency, increased reactive oxygen species production, and energy homeostasis in acute chagasic hearts. PBN and other mitochondria-targeted antioxidants may be useful in altering mitochondrial decay and oxidative pathology in Chagas' disease.

Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.

PubMed

Warren-Gash, Charlotte; Smeeth, Liam; Hayward, Andrew C

2009-10-01

Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15-1.76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

Antagonistic Effect of Atorvastatin on High Fat Diet Induced Survival during Acute Chagas Disease

PubMed Central

Zhao, Dazhi; Lizardo, Kezia; Cui, Min Hui; Ambadipudi, Kamalakar; Lora, Jose; Jelicks, Linda A; Nagajyothi, Jyothi F

2016-01-01

Chagasic cardiomyopathy, which is seen in Chagas Disease, is the most severe and life-threatening manifestation of infection by the kinetoplastid Trypanosoma cruzi. Adipose tissue and diet play a major role in maintaining lipid homeostasis and regulating cardiac pathogenesis during the development of Chagas cardiomyopathy. We have previously reported that T. cruzi has a high affinity for lipoproteins and that the invasion rate of this parasite increases in the presence of cholesterol, suggesting that drugs that inhibit cholesterol synthesis, such as statins, could affect infection and the development of Chagasic cardiomyopathy. The dual epidemic of diabetes and obesity in Latin America, the endemic regions for Chagas Disease, has led to many patients in the endemic region of infection having hyperlipidemia that is being treated with statins such as atorvastatin. The current study was performed to examine using mice fed on either regular or high fat diet the effect of atorvastatin on T. cruzi infection-induced myocarditis and to evaluate the effect of this treatment during infection on adipose tissue physiology and cardiac pathology. Atorvastatin was found to regulate lipolysis and cardiac lipidopathy during acute T. cruzi infection in mice and to enhance tissue parasite load, cardiac LDL levels, inflammation, and mortality in during acute infection. Overall, these data suggest that statins, such as atorvastatin, have deleterious effects during acute Chagas disease. PMID:27416748

[Sport for pacemaker patients].

PubMed

Israel, C W

2012-06-01

Sport activity is an important issue in many patients with a pacemaker either because they performed sport activities before pacemaker implantation to reduce the cardiovascular risk or to improve the course of an underlying cardiovascular disease (e.g. coronary artery disease, heart failure) by sports. Compared to patients with an implantable cardioverter defibrillator (ICD) the risks from underlying cardiovascular disease (e.g. ischemia, heart failure), arrhythmia, lead dysfunction or inappropriate therapy are less important or absent. Sport is contraindicated in dyspnea at rest, acute heart failure, new complex arrhythmia, acute myocarditis and acute myocardial infarction, valvular disease with indications for intervention and surgery and comorbidities which prevent physical activity. Patients with underlying cardiovascular disease (including hypertension) should preferably perform types and levels of physical activity that are aerobic (with dynamic exercise) such as running, swimming, cycling instead of sport with high anaerobic demands and high muscular workload. In heart failure, studies demonstrated advantages of isometric sport that increases the amount of muscle, thereby preventing cardiac cachexia. Sport with a risk of blows to the chest or physical contact (e.g. boxing, rugby, martial arts) should be avoided. Implantation, programming and follow-up should respect specific precautions to allow optimal physical activity with a pacemaker including implantation of bipolar leads on the side contralateral to the dominant hand, individual programming of the upper sensor and tracking rate and regular exercise testing.

Immunopathology of experimental Chagas' disease: binding of T cells to Trypanosoma cruzi-infected heart tissue.

PubMed Central

Mortatti, R C; Maia, L C; de Oliveira, A V; Munk, M E

1990-01-01

The immunopathology of Chagas' disease was studied in the experimental model of chronic infection in C57BL/10JT or mice. Sublethal infection with Trypanosoma cruzi, Y strain, induced specific antibodies and a delayed hypersensitivity response to parasite antigens. Mice developed chronic chagasic myocarditis but not skeletal muscle myositis. Binding of T cells to infected heart tissue was investigated during short-term cocultivation of lymphocytes with heart cryostat sections. T cells from infected mice and from normal controls bound equally to myocardium and liver sections from both infected and normal mice. A search in depth was attempted with cells heavily tagged with 99mTc. Labeled T cells from chagasic mice bound to both normal and infected myocardium slices. 99mTc-labeled T cells from controls gave the same binding values. Glass-adherent spleen cells behaved identically to T cells. Prior treatment of the tissue with serum from chronically infected mice did not increase the number of binding cells. Peritoneal macrophages tagged with 99mTc-sulfur colloid also bound to infected myocardium slices. The binding of macrophages was not changed by pretreatment of infected tissue with anti-T, cruzi antibodies. In short, this work did not detect any population of T cells or macrophages which could bind specifically to infected heart tissue to initiate an autoreactive process. Images PMID:2228230

Detection of non-polio enteroviruses in Hungary 2000-2008 and molecular epidemiology of enterovirus 71, coxsackievirus A16, and echovirus 30.

PubMed

Kapusinszky, Beatrix; Szomor, Katalin N; Farkas, Agnes; Takács, Mária; Berencsi, György

2010-04-01

Human enteroviruses are associated with various clinical syndromes from minor febrile illness to severe, potentially fatal conditions like aseptic meningitis, paralysis, myocarditis, and neonatal enteroviral sepsis. Between June 2000 and August 2008 echovirus (E) type 2, 4, 6, 7, 9, 11, 13, 25, 30, coxsackievirus (CV) -A16, -A19, -B5, and enterovirus 71 (EV71) were reported in Hungary. In this study, 29 previously enterovirus positive samples from 28 patients diagnosed with hand, foot and mouth disease, meningitis and encephalitis, were molecularly typed. The genetic relationships of identified serotypes CV-A16, EV71, and E30 were assessed by direct sequencing of genomic region encoding the capsid protein VP1. The sequences were compared to each other and sequences from other geographical regions possessed in Genbank. The phylogenetic analysis of CV-A16 revealed that the viruses were mostly of Far-Eastern or Asia-Pacific origin. Typing of EV71 showed that one virus from 2000 belonged to genotype C1 and five viruses observed in 2004 and 2005 were identified as genotype C4. The 11 echovirus 30 strains showed homology with those of neighbor European countries. The molecular examination of E30 revealed that three separate lineages circulated in 2000, 2001, and 2004-2006 in Hungary.

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

PubMed

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Elevated Endomyocardial Biopsy Macrophage-Related Markers in Intractable Myocardial Diseases.

PubMed

Hayashi, Yuka; Hanawa, Haruo; Jiao, Shuang; Hasegawa, Go; Ohno, Yukako; Yoshida, Kaori; Suzuki, Tomoyasu; Kashimura, Takeshi; Obata, Hiroaki; Tanaka, Komei; Watanabe, Tohru; Minamino, Tohru

2015-12-01

Tissue macrophages can be activated by endogenous danger signals released from cells that are stressed or injured, leading to infiltration of inflammatory macrophages and neutrophils. We postulated that macrophage-related markers might be closely associated with the existence of endogenous danger signals, reflecting ongoing tissue injury in the absence of foreign substances. This study was designed to assess the ability of macrophage-related markers in endomyocardial biopsies to predict ongoing cardiac injury in non-inflammatory myocardial diseases. We examined levels of macrophage-related markers (CD68, CD163, CD45) in endomyocardial biopsies from patients (n = 86) with various myocardial diseases by quantitative reverse transcription-polymerase chain reaction (n = 78) and immunohistochemistry (n = 56). Thirty-three patients without inflammatory cardiac disease such as myocarditis and sarcoidosis were classified as "improved" or "non-improved" defined as a 10% increase in left ventricular ejection fraction by echocardiograph and a value greater than 30% at the time of follow-up. All macrophage-related (MacR) markers levels were not higher in non-improved dilated cardiomyopathy (DCM) patients than improved patients. However, patients with cardiac amyloidosis, cardiac Fabry disease, mitochondrial cardiomyopathy, and biventricular arrhythmogenic right ventricular cardiomyopathy (ARVC), which were categorized as "non-improvement diseases," had elevated macrophage-related markers compared to improved patients. Macrophage-related markers levels were increased in endomyocardial biopsy samples of patients with intractable myocardial diseases such as amyloidosis, mitochondrial disease, Fabry disease, and biventricular ARVC.

Inappropriate bradycardia in Ebola virus disease.

PubMed

Cellarier, G; Bordes, J; De Greslan, T; Karkowski, L; Gagnon, N; Billhot, M; Cournac, J-M; Rousseau, C; Mac Nab, C; Dubrous, P

2016-08-01

As part of French assistance for the outbreak of Ebola virus disease in west Africa, a military treatment center for infected healthcare workers was deployed in Conakry, Guinea. Although some cases of bradycardia have been reported since the first Ebola outbreak, they have never been documented to our knowledge. We studied heart rhythm in patients with Ebola virus disease to analyze inappropriate bradycardia and discuss its mechanism. Nine patients who tested positive for Ebola were admitted in March 2015. Baseline clinical data were noted at admission and twice a day during follow-up, and laboratory analyses (with troponin testing) were performed. At admission, patients had no or moderate tachycardia (pulse = 82 ± 27 bpm). Among them, a 32-year-old midwife admitted on her fourth day of symptoms had marked bradycardia: 43 bpm. ECG showed sinus bradycardia with no conduction disturbances or repolarization anomalies; findings were similar for the three other patients with bradycardia (< 60 bpm). During follow-up, her pulse gradually increased, as it did for the other three; all four recovered. Despite several factors likely to promote tachycardia, we observed no or only moderate tachycardia in all patients with Ebola. In our study, ECG recorded sinus rhythm, without significant node dysfunction or atrioventricular block. In the absence of any evidence of myocarditis, we discuss the possibility of a central nervous system cause, associated with encephalitis. We observed relative or marked bradycardia in our patients infected with Ebola. We hypothesize that its causal mechanism was encephalitis.

Vegetative Valvular Endocarditis and Hepatitis Associated with Helcococcus ovis in a 7-year-old White Leghorn Rooster.

PubMed

Crispo, Manuela; Stoute, Simone; Savaris, Thaiza; Bickford, Arthur; Santoro, Tiffany; Sentíes-Cué, C Gabriel

2017-12-01

Helcococcus ovis is a slow-growing, pyridoxal-dependent, Gram-positive coccus belonging to the Peptostreptococcaceae family. Bacteria belonging to the genus Helcococcus are considered normal inhabitants of keratinized epithelium in humans; however, several reports support their role as pathogens in humans and several animal species. This case report describes the identification of H. ovis in a white leghorn rooster with valvular vegetative endocarditis and hepatitis. In February 2017 one dead, 7-yr-old, white leghorn rooster was submitted to the California Animal Health and Food Safety Turlock laboratory for diagnostic testing. Postmortem and microscopic examination revealed vegetative endocarditis and aortic thrombosis associated with large numbers of Gram-positive cocci. Myocarditis and extensive necrotic hepatitis were also noticed. Helcococcus ovis was isolated in large numbers from the aortic endothelium and confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Bacterial colonies become evident 48 hr postincubation and exhibited a satellite growth around Escherichia coli on blood agar plates. A similar relationship has been described between Helcococcus spp. and Staphylococcus aureus. The primary site of infection in this chicken was not determined. To our understanding this is the first report of H. ovis infection in an avian species. The fastidious nature and nutritional requirements of Helcococcus spp. must be considered in order to allow proper identification and avoid misdiagnosis. Further studies are needed to define pathogenesis, virulence factors, and predisposing conditions associated with this microorganism.

Curcumin and autoimmune disease.

PubMed

Bright, John J

2007-01-01

The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

Feline cardiomyopathy.

PubMed

Liu, S K; Tilley, L P; Lord, P F

1975-01-01

Cardiology was diagnosed by means of clinical, radiographic, electrocardiographic phonocardiographic, angiocardiographic, and pathological findings in 271 or 3,745 cats necropsied from January 1962 to April 1974. The affected cats can be divided into three groups on the basis of the gross and microscopic pathological lesions: 1)endocarditis and myocarditis in 20 young cats; 2)endomyocardial fibrosis and left ventricular hypertrophy in 182 cats; and 3)myocardial degeneration and biventricular dilatation in 69 cats. Of 271 affected cats, thromboembolus was observed in the aorta, and in the carotid, femoral, iliac, renal, pulmonary, and hepatic arteries in 104 instances. The important aspects of cardiomyopathy in cats appears to be the reduced diastolic compliance of the thick left ventricle, resulting in poor fillin. Resistance to ventricular inflow raises the diastolic pressure and causes compensatory left atrial enlargement. A pathogenesis for the onset of clinical signs at any stages as the cause of the heart disease is postulated on the basis of stress causing tachycardia and poor left ventricular filling. Acute left-sided failure with pulmonary edema may be precipitated. Approximately one-fourth of the cats have enlargement of all cardiac chambers, typical of congestive cardiomyopathy. On the basis of the close similarily to cardiomyopathy in man, the cat could serve as a suitable animal model for a conservation of time and effort in the attack against this disorder. There is a need for coordinated research programs for utilizing the multiple avenues of approach such as: epidemiological, clinical, biochemical, pathological, ultrastructural, virological, and immunological.

Next-generation endomyocardial biopsy: the potential of confocal and super-resolution microscopy.

PubMed

Crossman, David J; Ruygrok, Peter N; Hou, Yu Feng; Soeller, Christian

2015-03-01

Confocal laser scanning microscopy and super-resolution microscopy provide high-contrast and high-resolution fluorescent imaging, which has great potential to increase the diagnostic yield of endomyocardial biopsy (EMB). EMB is currently the gold standard for identification of cardiac allograft rejection, myocarditis, and infiltrative and storage diseases. However, standard analysis is dominated by low-contrast bright-field light and electron microscopy (EM); this lack of contrast makes quantification of pathological features difficult. For example, assessment of cardiac allograft rejection relies on subjective grading of H&E histology, which may lead to diagnostic variability between pathologists. This issue could be solved by utilising the high contrast provided by fluorescence methods such as confocal to quantitatively assess the degree of lymphocytic infiltrate. For infiltrative diseases such as amyloidosis, the nanometre resolution provided by EM can be diagnostic in identifying disease-causing fibrils. The recent advent of super-resolution imaging, particularly direct stochastic optical reconstruction microscopy (dSTORM), provides high-contrast imaging at resolution approaching that of EM. Moreover, dSTORM utilises conventional fluorescence dyes allowing for the same structures to be routinely imaged at the cellular scale and then at the nanoscale. The key benefit of these technologies is that the high contrast facilitates quantitative digital analysis and thereby provides a means to robustly assess critical pathological features. Ultimately, this technology has the ability to provide greater accuracy and precision to EMB assessment, which could result in better outcomes for patients.

[Toxoplasmosis peri-myocarditis as initial manifestation of highly malignant non-Hodgkin's lymphoma].

PubMed

Zweiker, R; Eber, B; Samonigg, H; Reisinger, E C; Kasparek, A; Schumacher, M; Fruhwald, F M; Apfelbeck, U; Klein, W

1994-03-01

A case report of a 28-year-old mother of two children with FUO is presented. Physical examination revealed an anemic and febrile woman, who lost 10 kg of weight during the past 3 months. Furthermore, two lymphatic nodes with diameters below 1 cm were detected at the neck and inguinal region. A search for origin of fever including evaluation of foci, malignancies and laboratory investigations was primarily unsuccessful. At day 7 after admission a pericardial murmur could be heard. Echocardiography revealed a pericardial effusion, which increased up to 4 cm during the following days, leading to hemodynamic impairment and asystole. Immediate CR was successful, pericardial effusion was aspirated. Looking for etiology of fever the presence of IgM-antibodies against toxoplasma gondii by an ELISA test was possible. Therefore, toxoplasmosis was diagnosed and a treatment-regimen comprising pyrimethamin and sulfadiazin was initiated. Because of the threat to life and very high titers of C-reactive protein, antibiotic therapy (imipenem) was given additionally. An immunologic impairment was excluded by normal ratio of CD4:CD8 of lymphocytes, normal HIV-test and a nonsuspicious Jamshidi-biopsy of the bone marrow. However, in week 9 after admission lymphatic node-tumors suddenly appeared at the neck and pulmonary hilus. After diagnostic exstirpation a malignant non-Hodgkin-lymphoma (T-cell-type) was diagnosed. It is concluded that in obscure pericardial effusion toxoplasmosis should be considered and that this manifestation may be a precursor of malignant non-Hodgkin-lymphoma.

First report of systemic toxoplasmosis in a New Zealand sea lion (Phocarctos hookeri).

PubMed

Roe, W D; Michael, S; Fyfe, J; Burrows, E; Hunter, S A; Howe, L

2017-01-01

A 1-year-old female New Zealand sea lion (Phocarctos hookeri) was intermittently observed in the Otago region of New Zealand over an 11-month period, always dragging her hind flippers. In December 2012 the sea lion was found dead, after a period of several days being observed to be harassed by male sea lions. At gross postmortem examination the sea lion was in moderate body condition with signs of recent bite wounds and bruising. The lungs were dark and poorly inflated. Histological findings included meningoencephalomyelitis, radiculomyelitis of the cauda equina, myocarditis and myositis. Toxoplasmosis gondii organisms were detected histologically and following immunohistochemistry in the brain, spinal cord, spinal nerves and pelvic muscles. Nested PCR analysis and sequencing confirmed the presence of T. gondii DNA in uterine and lung tissue. A variant type II T. gondii genotype was identified using multilocus PCR-restriction fragment length polymorphism analysis. Systemic toxoplasmosis. Infection with T. gondii involving the spinal cord and nerves was the likely cause of the paresis observed in this sea lion before death. Ultimately, death was attributed to crushing and asphyxiation by a male sea lion, presumably predisposed by impaired mobility. Diagnosis of toxoplasmosis in a New Zealand sea lion highlights the possibility that this disease could play a role in morbidity and mortality in this endangered species, particularly in the recently established mainland populations that are close to feline sources of T. gondii oocysts.

Involvement of substance P and the NK-1 receptor in human pathology.

PubMed

Muñoz, Miguel; Coveñas, Rafael

2014-07-01

The peptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems, but it is also present in cells not belonging to the nervous system (immune cells, liver, lung, placenta, etc.). SP is located in all body fluids, such as blood, cerebrospinal fluid, breast milk, etc. i.e. it is ubiquitous in human body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates many pathophysiological functions in the central nervous system, such as emotional behavior, stress, depression, anxiety, emesis, vomiting, migraine, alcohol addiction, seizures and neurodegeneration. SP has been also implicated in pain, inflammation, hepatitis, hepatotoxicity, cholestasis, pruritus, myocarditis, bronchiolitis, abortus, bacteria and viral infection (e.g., HIV infection) and it plays an important role in cancer (e.g., tumor cell proliferation, antiapoptotic effects in tumor cells, angiogenesis, migration of tumor cells for invasion, infiltration and metastasis). This means that the SP/NK-1 receptor system is involved in the molecular bases of many human pathologies. Thus, knowledge of this system is the key for a better understanding and hence a better management of many human diseases. In this review, we update the involvement of the SP/NK-1 receptor system in the physiopathology of the above-mentioned pathologies and we suggest valuable future therapeutic interventions involving the use of NK-1 receptor antagonists, particularly in the treatment of emesis, depression, cancer, neural degeneration, inflammatory bowel disease, viral infection and pruritus, in which that system is upregulated.

New Coxsackievirus 2Apro and 3Cpro protease antibodies for virus detection and discovery of pathogenic mechanisms.

PubMed

Laitinen, Olli H; Svedin, Emma; Kapell, Sebastian; Hankaniemi, Minna M; Larsson, Pär G; Domsgen, Erna; Stone, Virginia M; Määttä, Juha A E; Hyöty, Heikki; Hytönen, Vesa P; Flodström-Tullberg, Malin

2018-05-01

Enteroviruses (EVs), such as the Coxsackie B-viruses (CVBs), are common human pathogens, which can cause severe diseases including meningitis, myocarditis and neonatal sepsis. EVs encode two proteases (2A pro and 3C pro ), which perform the proteolytic cleavage of the CVB polyprotein and also cleave host cell proteins to facilitate viral replication. The 2A pro cause direct damage to the infected heart and tools to investigate 2A pro and 3C pro expression may contribute new knowledge on virus-induced pathologies. Here, we developed new antibodies to CVB-encoded 2A pro and 3C pro ; Two monoclonal 2A pro antibodies and one 3C pro antibody were produced. Using cells infected with selected viruses belonging to the EV A, B and C species and immunocytochemistry, we demonstrate that the 3C pro antibody detects all of the EV species B (EV-B) viruses tested and that the 2A pro antibody detects all EV-B viruses apart from Echovirus 9. We furthermore show that the new antibodies work in Western blotting, immunocyto- and immunohistochemistry, and flow cytometry to detect CVBs. Confocal microscopy demonstrated the expression kinetics of 2A pro and 3C pro , and revealed a preferential cytosolic localization of the proteases in CVB3 infected cells. In summary, the new antibodies detect proteases that belong to EV species B in cells and tissue using multiple applications. Copyright © 2018 Elsevier B.V. All rights reserved.

How to interpret liver function tests in heart failure patients?

PubMed

Çağlı, Kumral; Başar, Fatma Nurcan; Tok, Derya; Turak, Osman; Başar, Ömer

2015-05-01

Cardiac hepatopathy has generally been used to describe any liver damage caused by cardiac disorders in the absence of other possible causes of liver damage. Although there is no consensus on the terminology used, cardiac hepatopathy can be examined as congestive hepatopathy (CH) and acute cardiogenic liver injury (ACLI). CH is caused by passive venous congestion of the liver that generally occurs in the setting of chronic cardiac conditions such as chronic HF, constrictive pericarditis, tricuspid regurgitation, or right-sided heart failure (HF) of any cause, and ACLI is most commonly associated with acute cardiocirculatory failure resulting from acute myocardial infarction, acute decompensated HF, or myocarditis. Histologically, CH is characterized by sinusoidal dilation, replacement of hepatocytes with red blood cells extravasating from the sinusoids, and necrosis/apoptosis of zone 3 of the Rappaport acinus, and it could progress to cirrhosis in advanced cases. In ACLI, however, massive necrosis of zone 3 is the main histological finding. Primary laboratory findings of CH are elevated serum cholestasis markers including bilirubin, alkaline phosphatase, and γ-glutamyl-transpeptidase levels, whereas those of ACLI are a striking elevation in transaminase and lactate dehydrogenase levels. Both CH and ACLI have a prognostic value for identifying cardiovascular events and mortality and have some special implications in the management of patients undergoing ventricular assist device implantation or cardiac transplantation. There is no specific treatment for CH or ACLI other than treatment of the underlying cardiac disorder.

Laboratory-controlled Challenges of Nile Tilapia (Oreochromis niloticus) with Streptococcus agalactiae: Comparisons between Immersion, Oral, Intracoelomic and Intramuscular Routes of Infection.

PubMed

Soto, E; Zayas, M; Tobar, J; Illanes, O; Yount, S; Francis, S; Dennis, M M

2016-11-01

Streptococcus agalactiae, the aetiological agent of streptococcosis in fish, is an important pathogen of cultured and wild fish worldwide. To gain a better understanding of the pathogenesis of streptococcosis in Nile tilapia (Oreochromis niloticus), and to identify the experimental route of infection that most closely mimics natural disease, fingerlings were challenged with S. agalactiae utilizing different delivery methods. Fingerlings were challenged via intracoelomic injection (ICinj), intramuscular injection (IMinj), orally or by immersion with serial dilutions of S. agalactiae. The dose lethal to 50% of test fish 15 days post challenge was 120 colony forming units (CFU)/fish after ICinj, and 10 5  CFU/fish after IMinj. Acute mortalities were present in both groups, but were higher in the fish challenged by ICinj. Very low mortalities were observed in the fish challenged via oral or immersion routes. Post-mortem evaluation of survivors revealed classical lesions associated with fish streptococcosis, including granulomatous or lymphohistiocytic epicarditis, splenitis, meningitis, myocarditis, choroiditis and exophthalmia. The information obtained improves our understanding of the pathogenesis of streptococcosis in fish, and provides useful information regarding controlled experimental infections in tilapia challenged with S. agalactiae. Results from this study suggest that IMinj challenge methods are not only suitable to induce streptococcosis in tilapia, but they may be the preferred method to study the pathogenesis of the naturally-occurring disease in this species. Copyright © 2016 Elsevier Ltd. All rights reserved.

DISCOVERY OF THREE NOVEL COCCIDIAN PARASITES INFECTING CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS), WITH EVIDENCE OF SEXUAL REPLICATION AND INTERSPECIES PATHOGENICITY

PubMed Central

Colegrove, Kathleen M.; Grigg, Michael E.; Carlson-Bremer, Daphne; Miller, Robin H.; Gulland, Frances M. D.; Ferguson, David J. P.; Rejmanek, Daniel; Barr, Bradd C.; Nordhausen, Robert; Melli, Ann C.; Conrad, Patricia A.

2016-01-01

Enteric protozoal infection was identified in 5 stranded California sea lions (Zalophus californianus). Microscopically, the apical cytoplasm of distal jejunal enterocytes contained multiple stages of coccidian parasites, including schizonts with merozoites and spherical gametocytes, which were morphologically similar to coccidians. By histopathology, organisms appeared to be confined to the intestine and accompanied by only mild enteritis. Using electron microscopy, both sexual (microgametocytes, macrogamonts) and asexual (schizonts, merozoites) coccidian stages were identified in enterocytes within parasitophorous vacuoles, consistent with apicomplexan development in a definitive host. Serology was negative for tissue cyst-forming coccidians, and immunohistochemistry for Toxoplasma gondii was inconclusive and negative for Neospora caninum and Sarcocystis neurona. Analysis of ITS-1 gene sequences amplified from frozen or formalin-fixed paraffin-embedded intestinal sections identified DNA sequences with closest homology to Neospora sp. (80%); these novel sequences were referred to as belonging to coccidian parasites ‘‘A,’’ ‘‘B,’’ and ‘‘C.’’ Subsequent molecular analyses completed on a neonatal harbor seal (Phoca vitulina) with protozoal lymphadenitis, hepatitis, myocarditis, and encephalitis showed that it was infected with a coccidian parasite bearing the ‘‘C’’ sequence type. Our results indicate that sea lions likely serve as definitive hosts for 3 newly described coccidian parasites, at least 1 of which is pathogenic in a marine mammal intermediate host species. PMID:21495828

[Cardiovascular involvement in Behçet's disease].

PubMed

Desbois, A-C; Wechsler, B; Cluzel, P; Helft, G; Boutin, D; Piette, J-C; Cacoub, P; Saadoun, D

2014-02-01

Vascular involvement is a common complication of Behçet's disease (BD) and affects up to 40% of BD patients. These complications worsen the prognosis of BD. The concept of vasculo-Behçet has been adopted for cases in which vascular complications dominate the clinical features. Vascular manifestations affect particularly young men, during the first years following onset of the disease. Venous complications are the most frequent vascular complications, affecting 14 to 40% of BD patients. Superficial and deep lower limb thrombosis is the most frequent venous complications but one third of venous thrombosis concern large vessels (such as cerebral venous thrombosis, pulmonary embolism, and inferior or superior vena cava, etc.). Budd-Chiari syndrome is the worst prognostic factor increasing mortality by 9 times. Arterial complications (2 to 17% of BD patients) include aneurysms and occlusions/stenosis. Main locations of arterial lesions are aortic (abdominal and thoracic), femoral, pulmonary and iliac arteries. Aneurysms are the most severe arterial complications, particularly pulmonary aneurysms associated with a high risk of massive bleeding. Cardiac complications (up to 6% of BD patients) include pericarditis, endocardial lesions (aortic regurgitation and less often mitral insufficiency), myocardial lesions (myocardial infarction, myocarditis and endomyocardial fibrosis) and intracardiac thrombosis (right ventricle and atrium). Coronary lesions complicated to myocardial infarction are the most severe cardiac complications. Treatment is based on corticosteroids and immunosuppressive drugs. The use of anticoagulation in venous thrombosis is still controversial. Copyright © 2014. Published by Elsevier SAS.

Successful treatment with tacrolimus in TAFRO syndrome: two case reports and literature review.

PubMed

Shirai, Taiichiro; Onishi, Akira; Waki, Daisuke; Saegusa, Jun; Morinobu, Akio

2018-06-01

TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome. Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly. In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients' laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis. In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy. This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome.

A critical assessment of the association between postnatal toxoplasmosis and epilepsy in immune-competent patients.

PubMed

Uzorka, J W; Arend, S M

2017-07-01

While postnatal toxoplasmosis in immune-competent patients is generally considered a self-limiting and mild illness, it has been associated with a variety of more severe clinical manifestations. The causal relation with some manifestations, e.g. myocarditis, has been microbiologically proven, but this is not unequivocally so for other reported associations, such as with epilepsy. We aimed to systematically assess causality between postnatal toxoplasmosis and epilepsy in immune-competent patients. A literature search was performed. The Bradford Hill criteria for causality were used to score selected articles for each component of causality. Using an arbitrary but defined scoring system, the maximal score was 15 points (13 for case reports). Of 704 articles, five case reports or series and five case-control studies were selected. The strongest evidence for a causal relation was provided by two case reports and one case-control study, with a maximal causality score of, respectively, 9/13, 10/13 and 10/15. The remaining studies had a median causality score of 7 (range 5-9). No selection bias was identified, but 6/10 studies contained potential confounders (it was unsure whether the infection was pre- or postnatal acquired, or immunodeficiency was not specifically excluded). Based on the evaluation of the available literature, although scanty and of limited quality, a causal relationship between postnatal toxoplasmosis and epilepsy seems possible. More definite proof requires further research, e.g. by performing Toxoplasma serology in all de novo epilepsy cases.

Scrub Typhus in Northeastern Thailand: Eschar Distribution, Abnormal Electrocardiographic Findings, and Predictors of Fatal Outcome.

PubMed

Thipmontree, Wilawan; Tantibhedhyangkul, Wiwit; Silpasakorn, Saowaluk; Wongsawat, Ekkarat; Waywa, Duangdao; Suputtamongkol, Yupin

2016-10-05

Scrub typhus is endemic in Thailand. Of the 495 patients with acute undifferentiated fever studied in Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima, Thailand, from June 1, 2011, to December 31, 2012, 146 patients (29.5%) had confirmed scrub typhus. The majority of cases were male, farmers, with the mean (±standard deviation) age of 54.1 ± 15.2 years. A total of 59 patients (40.4%) had eschar lesion. The commonest sites for an eschar in male patients were the perineum, inguinal, and buttock area; whereas in females, it was the head and neck area. Abnormal electrocardiogram was found in 39 of 79 patients (49.4%) with sinus tachycardia being the most frequent finding (17, 21.5%). A total of 73 patients (50%) had at least one complication. Myocarditis was the cause of complete heart block in a scrub typhus patient, and he fully recovered after receiving intravenous chloramphenicol treatment. The case fatality rate was 6.2% (nine deaths).The independent predictors for fatal outcome were age over 65 years (odds ratio [OR] = 14.49, 95% confidence interval [CI] = 1.26-166.44, P = 0.03), acute kidney injury (OR = 12.75, 95% CI = 1.77-92.07, P = 0.01), and hyperbilirubinemia (OR = 24.82, 95% CI = 2.12-286.61, P = 0.01). Early diagnosis and prompt appropriate treatment can improve the patient's outcome. © The American Society of Tropical Medicine and Hygiene.

Molecular Epidemiology of Human Oral Chagas Disease Outbreaks in Colombia

PubMed Central

Ramírez, Juan David; Montilla, Marleny; Cucunubá, Zulma M.; Floréz, Astrid Carolina; Zambrano, Pilar; Guhl, Felipe

2013-01-01

Background Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI). In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. Methodology and Principal Findings High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing) and mtMLST (mitochondrial Multilocus Sequence Typing) strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. Conclusions These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed. PMID:23437405

Utility of late gadolinium enhancement in pediatric cardiac MRI.

PubMed

Etesami, Maryam; Gilkeson, Robert C; Rajiah, Prabhakar

2016-07-01

Late gadolinium enhancement (LGE) cardiac magnetic resonance (MR) imaging sequence is increasingly used in the evaluation of pediatric cardiovascular disorders, and although LGE might be a normal feature at the sites of previous surgeries, it is pathologically seen as a result of extracellular space expansion, either from acute cell damage or chronic scarring or fibrosis. LGE is broadly divided into ischemic and non-ischemic patterns. LGE caused by myocardial infarction occurs in a vascular distribution and always involves the subendocardial portion, progressively involving the outer regions in a waveform pattern. Non-ischemic cardiomyopathies can have a mid-myocardial (either linear or patchy), subepicardial or diffuse subendocardial distribution. Idiopathic dilated cardiomyopathy can have a linear mid-myocardial pattern, while hypertrophic cardiomyopathy can have fine, patchy enhancement in hypertrophied and non-hypertrophied segments as well as right ventricular insertion points. Myocarditis and sarcoidosis have a mid-myocardial or subepicardial pattern of LGE. Fabry disease typically affects the basal inferolateral segment while Danon disease typically spares the septum. Pericarditis is characterized by diffuse or focal pericardial thickening and enhancement. Thrombus, the most common non-neoplastic cardiac mass, is characterized by absence of enhancement in all sequences, while neoplastic masses show at least some contrast enhancement, depending on the pathology. Regardless of the etiology, presence of LGE is associated with a poor prognosis. In this review, we describe the technical modifications required for performing LGE cardiac MR sequence in children, review and illustrate the patterns of LGE in children, and discuss their clinical significance.

MRI-based evidence for myocardial involvement in women with hypereosinophilic syndrome.

PubMed

Miszalski-Jamka, Tomasz; Szczeklik, Wojciech; Karwat, Krzysztof; Sokołowska, Barbara; Gąsior, Jolanta; Rucińska, Małgorzata; Mazur, Wojciech; Skotnicki, Aleksander; Kereiakes, Dean J; Urbańczyk, Małgorzata; Jaźwiec, Przemysław; Musiał, Jacek

2015-01-01

The aim of the study was to assess the presence and spectrum of cardiac abnormalities identified by cardiac magnetic resonance (CMR) in women with hypereosinophilic syndrome (HES) of undefined etiology, who present with normal electrocardiography (ECG) and transthoracic echocardiography (TTE) and no history of heart disease. Ten women (mean age, 48 ± 14 years) with HES of undefined etiology, normal ECG and TTE, and no history of heart disease underwent CMR. CMR showed cardiac abnormalities in 6 subjects. Five patients had nonischemic late gadolinium enhancement (LGE) lesions within the left ventricular (LV) myocardium, and 3 patients demonstrated CMR evidence of myocardial inflammation. The LV ejection fraction was 68.5 ± 5.7%, and the end-diastolic volume index was 62.7 ± 14.7 mL/m(2). The maximum measured blood eosinophil count correlated with LVLGE volume (r = 0.80, P = 0.006) and was 11374 ± 6242 cells/μL and 4114 ± 2972 cells/μL (P = 0.047) in patients with and without LGE lesions, respectively. The actual blood eosinophil count in subjects with and without CMR evidence of myocarditis was 1058 ± 520 cells/μL and 354 ± 377 cells/μL (P = 0.04), respectively. Despite normal ECG, TTE, and absence of history of heart disease, women with HES of unknown etiology frequently demonstrate cardiac abnormalities on CMR, the presence and extent of which are related to blood eosinophil count.

Clinical cardiac regenerative studies in children.

PubMed

Pavo, Imre J; Michel-Behnke, Ina

2017-02-26

Although the incidence of pediatric heart failure is low, the mortality is relatively high, with severe clinical symptoms requiring repeated hospitalization or intensive care treatment in the surviving patients. Cardiac biopsy specimens have revealed a higher number of resident human cardiac progenitor cells, with greater proliferation and differentiation capacity, in the neonatal period as compared with adults, demonstrating the regeneration potential of the young heart, with rising interest in cardiac regeneration therapy in critically ill pediatric patients. We review here the available literature data, searching the MEDLINE, Google Scholar and EMBASE database for completed, and www.clinicaltrials.gov homepage for ongoing studies involving pediatric cardiac regeneration reports. Because of difficulties conducting randomized blinded clinical trials in pediatric patients, mostly case reports or cohort studies with a limited number of individuals have been published in the field of pediatric regenerative cardiology. The majority of pediatric autologous cell transplantations into the cardiac tissue have been performed in critically ill children with severe or terminal heart failure. Congenital heart disease, myocarditis, and idiopathic hypertrophic or dilated cardiomyopathy leading to congestive heart failure are some possible areas of interest for pediatric cardiac regeneration therapy. Autologous bone marrow mononuclear cells, progenitor cells, or cardiospheres have been applied either intracoronary or percutaneously intramyocardially in severely ill children, leading to a reported clinical benefit of cell-based cardiac therapies. In conclusion, compassionate use of autologous stem cell administration has led to at least short-term improvement in heart function and clinical stability in the majority of the critically ill pediatric patients.

In and ex-vivo Myocardial Tissue Temperature Monitoring by Combined Infrared and Ultrasonic Thermometries

NASA Astrophysics Data System (ADS)

Engrand, C.; Laux, D.; Ferrandis, J.-Y.; Sinquet, J.-C.; Demaria, R.; Le Clézio, E.

The success of cardiac surgery essentially depends on tissue preservation during intervention. Consequently a hypothermic cardio-plegia is applied in order to avoid ischemia. However, myocardial temperature is not monitored during operation. The aim of this study is then to find a relevant and simple method for myocardial global temperature estimation in real time using both ultrasounds and infra-red thermography. In order to quantify the sensitivity of ultrasonic velocity to temperature, a 2.25 MHz ultrasonic probe was used for ex-vivo tests. Pig myocards (n=25) were placed in a thermostatically-controlled water bath and measurements of the ultrasound velocity were realized from 10 to 30 ˚C. The results of this study indicate that the specificity and sensitivity of the ultrasonic echo delay induced by the modification of temperature can be exploited for in-depth thermometry. In parallel, for TIR experiments, a bolometer was used to detect the myocardium surface thermal evolution during in-vivo pig heart experiments. Hypothermic cardioplegic solutions were injected and infra-red surface imaging was performed during one hour. In the near futur, the correlation of the ultrasound and the infrared measurements should allow the real time estimation of the global temperature of the heart. The final objective being to realize in vivo measurements on human hearts, this information may have a very high importance in terms of per-operation inspection as well as decision making process during medical interventions.

Hsp70-1: upregulation via selective phosphorylation of heat shock factor 1 during coxsackieviral infection and promotion of viral replication via the AU-rich element.

PubMed

Qiu, Ye; Ye, Xin; Hanson, Paul J; Zhang, Huifang Mary; Zong, Jeff; Cho, Brian; Yang, Decheng

2016-03-01

Coxsackievirus B3 (CVB3) is the primary pathogen of viral myocarditis. Upon infection, CVB3 exploits the host cellular machineries, such as chaperone proteins, to benefit its own infection cycles. Inducible heat shock 70-kDa proteins (Hsp70s) are chaperone proteins induced by various cellular stress conditions. The internal ribosomal entry site (IRES) within Hsp70 mRNA allows Hsp70 to be translated cap-independently during CVB3 infection when global cap-dependent translation is compromised. The Hsp70 protein family contains two major members, Hsp70-1 and Hsp70-2. This study showed that Hsp70-1, but not Hsp70-2, was upregulated during CVB3 infection both in vitro and in vivo. Then a novel mechanism of Hsp70-1 induction was revealed in which CaMKIIγ is activated by CVB3 replication and leads to phosphorylation of heat shock factor 1 (HSF1) specifically at Serine 230, which enhances Hsp70-1 transcription. Meanwhile, phosphorylation of Ser230 induces translocation of HSF1 from the cytoplasm to nucleus, thus blocking the ERK1/2-mediated phosphorylation of HSF1 at Ser307, a negative regulatory process of Hsp70 transcription, further contributing to Hsp70-1 upregulation. Finally, we demonstrated that Hsp70-1 upregulation, in turn, stabilizes CVB3 genome via the AU-rich element (ARE) harbored in the 3' untranslated region of CVB3 genomic RNA.

The Chinese Herbal Medicine Sophora flavescens Activates Pregnane X Receptor

PubMed Central

Wang, Laiyou; Li, Feng; Lu, Jie; Li, Guodong; Li, Dan; Zhong, Xiao-bo; Guo, Grace L.

2010-01-01

Sophora flavescens (SF) is an herbal medicine widely used for the treatment of viral hepatitis, cancer, viral myocarditis, gastrointestinal hemorrhage, and skin diseases. It was recently reported that SF up-regulates CYP3A expression. The mechanism of SF-induced CYP3A expression is unknown. In the current study, we tested the hypothesis that SF-induced CYP3A expression is mediated by the activation of pregnane X receptor (PXR). We used two cell lines, DPX2 and HepaRG, to investigate the role of PXR in SF-induced CYP3A expression. The DPX2 cell line is derived from HepG2 cells with the stable transfection of human PXR and a luciferase reporter gene linked with a human PXR response element identified in the CYP3A4 gene promoter. In DPX2 cells, SF activated PXR in a concentration-dependent manner. We used a metabolomic approach to identify the chemical constituents in SF, which were further analyzed for their effect on PXR activation and CYP3A regulation. One chemical in SF, N-methylcytisine, was identified as an individual chemical that activated PXR. HepaRG is a highly differentiated hepatoma cell line that mimics human hepatocytes. In HepaRG cells, N-methylcytisine significantly induced CYP3A4 expression, and this induction was suppressed by the PXR antagonist sulforaphane. These results suggest that SF induces CYP3A expression via the activation of PXR. PMID:20736322

Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction.

PubMed

Ferreira, Ludmila Rodrigues Pinto; Ferreira, Frederico Moraes; Nakaya, Helder Imoto; Deng, Xutao; Cândido, Darlan da Silva; de Oliveira, Lea Campos; Billaud, Jean-Noel; Lanteri, Marion C; Rigaud, Vagner Oliveira-Carvalho; Seielstad, Mark; Kalil, Jorge; Fernandes, Fabio; Ribeiro, Antonio Luiz P; Sabino, Ester Cerdeira; Cunha-Neto, Edecio

2017-02-01

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Enterovirus infections in hospitals of Ile de France region over 2013.

PubMed

Molet, Lucie; Saloum, Kenda; Marque-Juillet, Stéphanie; Garbarg-Chenon, Antoine; Henquell, Cécile; Schuffenecker, Isabelle; Peigue-Lafeuille, Hélène; Rozenberg, Flore; Mirand, Audrey

2016-01-01

The monitoring and genotyping of Enterovirus (EV) infections can help to associate particular or severe clinical manifestations with specific EV types and to identify the aetiology of infectious outbreaks. To describe the epidemiological features of EV infections diagnosed during the year 2013 in the Greater Paris area (Ile de France). During 2013, 2497 samples taken from 470 patients in 33 hospitals of Ile-de France were tested for EV genome by RT-PCR. EV genotyping was performed by the National Reference Centre (NRC) laboratories. EV infections were retrospectively reviewed by retrieving clinical and genotyping data from the NRC database. Of the 2497 samples, 490 (19.6%) was positive for EV genome detection. These EV infections represented 88.7% and 24.1%, respectively, of all reported regional and national infections. Twenty-seven different genotypes were identified. Echovirus 30 (E-30) accounted for 54.1% of all characterized strains and caused a large outbreak. Four severe neonatal infections were reported, of which two were caused by EV-A71. Respiratory infections involving EV-D68 were observed in two adults. One fatal case of Coxsackievirus A2-associated myocarditis was reported. Monitoring EV infections in combination with EV genotyping via the French EV network characterized the epidemiology of EV infections in the Ile de France region in 2013 and documented severe EV infections associated with EV-A71 or CV-A2. Copyright © 2015 Elsevier B.V. All rights reserved.

Anticipating smallpox and monkeypox outbreaks: complications of the smallpox vaccine.

PubMed

Abrahams, Brian C; Kaufman, David M

2004-09-01

The recent outbreak in the Midwest of monkeypox, as well as the continued fears of a terrorist-induced epidemic of smallpox, prompted the authors' review of the literature regarding past and current experiences with smallpox vaccination. The smallpox vaccine, which is highly effective in preventing the spread of both these orthopoxvirus infectious illnesses, might be administered to numerous health care workers and, in the event of a smallpox attack, millions of other citizens. However, vaccinees would be at risk for several vaccine-related neurologic complications. According to prior reports, neurologic complications have occurred in 2.5 per million US individuals, with the most common being postvaccinal encephalomyelitis (PVEM). In older children and adults, PVEM causes stupor and coma, seizures, paraparesis, and other neurologic and mental abnormalities, and, in 16% of cases, permanent neurologic sequelae. The overall mortality rate of neurologic complications is approximately 1.5 per million vaccinees. Risk factors for PVEM were age younger than 1 year and no previous smallpox vaccination, but not a prior episode of PVEM or other preexisting neurologic illnesses. Neither the current smallpox vaccination campaigns in Israel nor the one in the United States has had comparable complications, but the US campaign has been associated with myocarditis and myopericarditis. Although the potential neurologic complications of the smallpox vaccine must be weighed against the threat of monkeypox and smallpox, current experience with vaccination suggests it carries a very low risk of neurologic complications and does not lead to exacerbations of chronic neurologic illnesses.

Myocardial recovery in peripartum cardiomyopathy: prospective comparison with recent onset cardiomyopathy in men and nonperipartum women.

PubMed

Cooper, Leslie T; Mather, Paul J; Alexis, Jeffrey D; Pauly, Daniel F; Torre-Amione, Guillermo; Wittstein, Ilan S; Dec, G William; Zucker, Mark; Narula, Jagat; Kip, Kevin; McNamara, Dennis M

2012-01-01

Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 (P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 (P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months. Copyright © 2012 Elsevier Inc. All rights reserved.

Atherosclerosis and central adiposity in a pediatric patient with AIDS treated with HAART: autopsy findings.

PubMed

Quijano, Graciela; Drut, Ricardo

2006-01-01

Several types of cardiovascular lesions may develop in pediatric human immunodeficiency virus-positive (HIV+)/acquired immunodeficiency syndrome (AIDS) patients, namely myocarditis, dilated cardiomyopathy, pericardial effusion, pericarditis, left ventricle hypertrophy, fibrocalcific arteriopathy, and aneurysms. Additional lesions may be discovered by histological examination. These include fibrocalcific lesions in medium-sized arteries and small vessels, mainly of the heart and brain, and vasculitis. In the large arteries the vasa vasorum may present chronic inflammatory infiltrates or leukocytoclastic vasculitis, resulting in aneurysms. We are reporting the case of a 14-year-old girl with mother-to-infant HIV transmission with a long history of several central nervous system infections and AIDS dementia, who received treatment with the HAART protocol (including a protease inhibitor) for 3 years. A year after beginning this treatment, cholesterol serum levels were 2.8 g/L and 3.8 g/L. Autopsy findings showed gross and microscopic features of adult-type atherosclerosis involving the whole thoracic aorta, its main branches, and the coronary arteries. Remarkably, the abdominal aorta and all its branches were almost completely devoid of these lesions. At the same time, although the body presented extreme cachexia, there were obvious subepericardial, periadrenal, and peripancreatic fat deposits. The referred findings may have resulted from the well-known metabolic-dyslipemic syndrome induced by the HAART therapy and have not been specifically mentioned previously in the literature in the particular setting observed in the case of this patient.

Cumulative childhood stress and autoimmune diseases in adults.

PubMed

Dube, Shanta R; Fairweather, DeLisa; Pearson, William S; Felitti, Vincent J; Anda, Robert F; Croft, Janet B

2009-02-01

To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p < .05). Compared with persons with no ACEs, persons with >or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p < .05). Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.

N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus

PubMed Central

Liao, Tang-Dong; Nakagawa, Pablo; Janic, Branislava; D'Ambrosio, Martin; Worou, Morel E.; Peterson, Edward L.; Rhaleb, Nour-Eddine; Yang, Xiao-Ping

2015-01-01

Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis, and end-organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e., Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis, Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 wk had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5, and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP-treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1, and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system. PMID:25740596

A model of horizontal and vertical integration of teaching on the cadaveric heart.

PubMed

Alsaggaf, Samar; Ali, Soad Shaker; Ayuob, Nasra Naeim; Eldeek, Basem Salama; El-Haggagy, Amira

2010-12-20

This work was performed in a trial to organize the learning process by focusing on the integration of medical education particularly between the three main subjects: gross anatomy, histology and pathology. It was a theoretical teaching draft designed to be implemented with second year students of the Medical school of the King Abdul Aziz University, Jeddah, KSA, in order to overcome disadvantages in traditional teaching. The objectives of this work were to make medical students, at the pre-clinical stage of their medical carrier, alert to diagnosis and handling of clinical problems and to develop their ability to integrate pre-clinical and clinical subjects. Fifty human cadaveric hearts were anatomically and histopathologically examined. This examination revealed six different clinical problems such as pericarditis, myocarditis, cardiac hypertrophy, parasitic infestation, rheumatic heart disease and fatty infiltration. The medical students of the second year will be first introduced to the normal anatomical and histological structure of the heart, then allowed to visualize and examine the specimens of the cadaveric heart both macroscopically and microscopically. They will be introduced to a set of clinical problems through some clinical scenarios and asked to search for the possible etiological factors causing these changes, associated signs and symptoms. Finally they will be asked to present their findings and interpretations. This paper demonstrated a pathway of self-directed learning in an integrated teaching setting in the medical curriculum using available cadaveric material at a preparatory stage before developing the system-based curriculum. 2010 Elsevier GmbH. All rights reserved.

Inhibition of coxsackievirus B3 replication by small interfering RNAs requires perfect sequence match in the central region of the viral positive strand.

PubMed

Yuan, Ji; Cheung, Paul K M; Zhang, Huifang M; Chau, David; Yang, Decheng

2005-02-01

Coxsackievirus B3 (CVB3) is the most common causal agent of viral myocarditis, but existing drug therapies are of limited value. Application of small interfering RNA (siRNA) in knockdown of gene expression is an emerging technology in antiviral gene therapy. To investigate whether RNA interference (RNAi) can protect against CVB3 infection, we evaluated the effects of RNAi on viral replication in HeLa cells and murine cardiomyocytes by using five CVB3-specific siRNAs targeting distinct regions of the viral genome. The most effective one is siRNA-4, targeting the viral protease 2A, achieving a 92% inhibition of CVB3 replication. The specific RNAi effects could last at least 48 h, and cell viability assay revealed that 90% of siRNA-4-pretreated cells were still alive and lacked detectable viral protein expression 48 h postinfection. Moreover, administration of siRNAs after viral infection could also effectively inhibit viral replication, indicating its therapeutic potential. Further evaluation by combination found that no enhanced inhibitory effects were observed when siRNA-4 was cotransfected with each of the other four candidates. In mutational analysis of the mechanisms of siRNA action, we found that siRNA functions by targeting the positive strand of virus and requires a perfect sequence match in the central region of the target, but mismatches were more tolerated near the 3' end than the 5' end of the antisense strand. These findings reveal an effective target for CVB3 silencing and provide a new possibility for antiviral intervention.

Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy

PubMed Central

Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Veeraveedu, Punniyakoti T; Nakamura, Takashi; Arozal, Wawaimuli; Sari, Flori R; Giridharan, Vijayasree V; Soetikno, Vivian; Palaniyandi, Suresh S; Harima, Meilei; Suzuki, Kenji; Nagata, Masaki; Kodama, Makoto; Watanabe, Kenichi

2012-01-01

Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47phox, p67phox, gp91phox and Nox4), fibrosis markers (TGF-β1 and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis. PMID:22268705

Recreational phenethylamine poisonings reported to a French poison control center.

PubMed

Le Roux, Gaël; Bruneau, Chloé; Lelièvre, Bénédicte; Bretaudeau Deguigne, Marie; Turcant, Alain; Harry, Patrick; Boels, David

2015-09-01

Over the last decade, use of phenethylamines has become increasingly prevalent. This study aimed to describe typical aspects of phenethylamine poisoning in order to better inform patient care. Phenethylamine poisoning cases reported to the Poison Control Center of Angers, France, from January, 2007 to December, 2013 were examined. Clinical findings were examined in 105 patients, including phenethylamine used, symptoms and final outcome. Patients were predominantly male (80%), with mean age 26±8 years. MDMA (38%), amphetamine (18%) and methamphetamine (14%) were the most commonly reported. Synthetic cathinones (10%) and the 2C series (7%) were also found. Substances most commonly associated with phenethylamine poisoning were cannabis (27%), ethanol (20%) and cocaine (9%). The most frequently reported symptoms included anxiety and hallucinations (49%), mydriasis and headache (41%), tachycardia (40%) and hypertension (15%). Complications such as seizures (7%), cardiac arrest (5%), toxic myocarditis (1%) and hemorrhagic stroke (1%) were also observed. Of the cases, the Poison Severity Score was: null or low, 66%, moderate, 21%, severe or fatal, 13%. Of the patients, 77% received hospital care and 12.4% were admitted to an intensive care unit. Analytical confirmations were obtained for all severe cases. While 93% of patients recovered, there were 5 deaths and 2 patients presented with neurological sequelae. Phenethylamine poisonings may be severe in young and healthy individuals. Physicians, toxicologists and analysts should be aware of new phenethylamine consumption trends in order to inform management of patient care and to contribute to a more responsive drug policy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The pathophysiology of heart failure.

PubMed

Kemp, Clinton D; Conte, John V

2012-01-01

Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

Influence of mitochondrion-toxic agents on the cardiovascular system.

PubMed

Finsterer, Josef; Ohnsorge, Peter

2013-12-01

Cardiovascular disease may be induced or worsened by mitochondrion-toxic agents. Mitochondrion-toxic agents may be classified as those with or without a clinical effect, those which induce cardiac disease only in humans or animals or both, as prescribed drugs, illicit drugs, exotoxins, or nutritiants, as those which affect the heart exclusively or also other organs, as those which are effective only in patients with a mitochondrial disorder or cardiac disease or also in healthy subjects, or as solid, liquid, or volatile agents. In humans, cardiotoxic agents due to mitochondrial dysfunction include anthracyclines (particularly doxorubicin), mitoxantrone, cyclophosphamide, cisplatin, fluorouracil, imatinib, bortezomib, trastuzumab, arsenic trioxide, cyclosporine-A, zidovudine, lamotrigine, glycosides, lidocain, isoproterenol, nitroprusside, pivalic acid, alcohol, cocaine, pesticides, cadmium, mycotoxins, cyanotoxins, meat meal, or carbon monoxide. Even more agents exhibit cardiac abnormalities due to mitochondrion-toxicity only in animals or tissue cultures. The mitochondrion-toxic effect results from impairment of the respiratory chain, the oxidative phosphorylation, the Krebs cycle, or the β-oxidation, from decrease of the mitochondrion-membrane potential, from increased oxidative stress, reduced anti-oxidative capacity, or from induction of apoptosis. Cardiac abnormalities induced via these mechanisms include cardiomyopathy, myocarditis, coronary heart disease, arrhythmias, heart failure, or Takotsubo syndrome. Discontinuation of the cardiotoxic agent results in complete recovery in the majority of the cases. Antioxidants and nutritiants may be of additional help. Particularly coenzyme-Q, riboflavin, vitamin-E, vitamin-C, L-carnitine, vitamin-D, thiamin, folic acid, omega-3 fatty acids, and D-ribose may alleviate mitochondrial cardiotoxic effects. Copyright © 2013 Elsevier Inc. All rights reserved.

Cardiac Gab1 deletion leads to dilated cardiomyopathy associated with mitochondrial damage and cardiomyocyte apoptosis

PubMed Central

Zhao, J; Yin, M; Deng, H; Jin, F Q; Xu, S; Lu, Y; Mastrangelo, M A; Luo, H; Jin, Z G

2016-01-01

A vital step in the development of heart failure is the transition from compensatory cardiac hypertrophy to decompensated dilated cardiomyopathy (DCM) during cardiac remodeling under mechanical or pathological stress. However, the molecular mechanisms underlying the development of DCM and heart failure remain incompletely understood. In the present study, we investigate whether Gab1, a scaffolding adaptor protein, protects against hemodynamic stress-induced DCM and heat failure. We first observed that the protein levels of Gab1 were markedly reduced in hearts from human patients with DCM and from mice with experimental viral myocarditis in which DCM developed. Next, we generated cardiac-specific Gab1 knockout mice (Gab1-cKO) and found that Gab-cKO mice developed DCM in hemodynamic stress-dependent and age-dependent manners. Under transverse aorta constriction (TAC), Gab1-cKO mice rapidly developed decompensated DCM and heart failure, whereas Gab1 wild-type littermates exhibited adaptive left ventricular hypertrophy without changes in cardiac function. Mechanistically, we showed that Gab1-cKO mouse hearts displayed severe mitochondrial damages and increased cardiomyocyte apoptosis. Loss of cardiac Gab1 in mice impaired Gab1 downstream MAPK signaling pathways in the heart under TAC. Gene profiles further revealed that ablation of Gab1 in heart disrupts the balance of anti- and pro-apoptotic genes in cardiomyocytes. These results demonstrate that cardiomyocyte Gab1 is a critical regulator of the compensatory cardiac response to aging and hemodynamic stress. These findings may provide new mechanistic insights and potential therapeutic target for DCM and heart failure. PMID:26517531

Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1

PubMed Central

Deng, Haoyu; Fung, Gabriel; Shi, Junyan; Xu, Suowen; Wang, Chen; Yin, Meimei; Hou, Jun; Zhang, Jingchun; Jin, Zheng-Gen; Luo, Honglin

2015-01-01

Coxsackievirus B3 (CVB3), an important human causative pathogen for viral myocarditis, pancreatitis, and meningitis, has evolved different strategies to manipulate the host signaling machinery to ensure successful viral infection. We previously revealed a crucial role for the ERK1/2 signaling pathway in regulating viral infectivity. However, the detail mechanism remains largely unknown. Grb2-associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction. In this study, we demonstrated that GAB1 was proteolytically cleaved after CVB3 infection at G175 and G436 by virus-encoded protease 2Apro, independent of caspase activation. Knockdown of GAB1 resulted in a significant reduction of viral protein expression and virus titers. Moreover, we showed that virus-induced cleavage of GAB1 is beneficial to viral growth as the N-terminal proteolytic product of GAB1 (GAB1-N1–174) further enhances ERK1/2 activation and promotes viral replication. Our results collectively suggest that CVB3 targets host GAB1 to generate a GAB1-N1–174 fragment that enhances viral infectivity, at least in part, via activation of the ERK pathway. The findings in this study suggest a novel mechanism that CVB3 employs to subvert the host signaling and facilitate consequent viral replication.—Deng, H., Fung, G., Shi, J., Xu, S., Wang, C., Yin, M., Hou, J., Zhang, J., Jin, Z.-G., Luo, H. Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1. PMID:26183772

Takotsubo cardiomyopathy associated with Miller-Fisher syndrome.

PubMed

Gill, Dalvir; Liu, Kan

2017-07-01

51-year-old female who presented with progressive paresthesia, numbness of the lower extremities, double vision, and trouble walking. Physical exam was remarkable for areflexia, and ptosis. Her initial EKG showed nonspecific ST segment changes and her Troponin T was elevated to 0.41ng/mL which peaked at 0.66ng/mL. Echocardiogram showed a depressed left ventricular ejection fraction to 35% with severely hypokinetic anterior wall and left ventricular apex was severely hypokinetic. EMG nerve conduction study showed severely decreased conduction velocity and prolonged distal latency in all nerves consistent with demyelinating disease. She was treated with 5days of intravenous immunoglobulin therapy to which she showed significant improvement in strength in her lower extremities. Echocardiogram repeated 4days later showing an improved left ventricular ejection fraction of 55% and no left ventricular wall motion abnormalities. Takotsubo cardiomyopathy is a rare complication of Miller-Fisher syndrome and literature review did not reveal any cases. Miller-Fisher syndrome is an autoimmune process that affects the peripheral nervous system causing autonomic dysfunction which may involve the heart. Due to significant autonomic dysfunction in Miller-Fisher syndrome, it could lead to arrhythmias, blood pressure changes, acute coronary syndrome and myocarditis, Takotsubo cardiomyopathy can be difficult to distinguish. The treatment of Takotsubo cardiomyopathy is supportive with beta-blockers and angiotensin-converting enzyme inhibitors are recommended until left ventricle ejection fraction improvement. Takotsubo cardiomyopathy is a rare complication during the acute phase of Miller-Fisher syndrome and must be distinguished from autonomic dysfunction as both diagnoses have different approaches to treatment. Published by Elsevier Inc.

Disseminated toxoplasmosis in Antillean manatees Trichechus manatus manatus from Puerto Rico.

PubMed

Bossart, Gregory D; Mignucci-Giannoni, Antonio A; Rivera-Guzman, Antonio L; Jimenez-Marrero, Nilda M; Camus, Alvin C; Bonde, Robert K; Dubey, Jitender P; Reif, John S

2012-11-08

Necropsies were conducted on 4 Antillean manatees Trichechus manatus manatus that were stranded in single events on the coastal beaches of Puerto Rico from August 2010 to August 2011. Three manatees were emaciated and the gastrointestinal tracts were devoid of digesta. Microscopically, all manatees had severe widespread inflammatory lesions of the gastrointestinal tract and heart with intralesional tachyzoites consistent with Toxoplasma gondii identified by histological, ultrastructural and immunohistochemical techniques. The gastrointestinal lesions included severe, multifocal to diffuse, chronic-active enteritis, colitis and/or gastritis often with associated ulceration, necrosis and hemorrhage. Enteric leiomyositis was severe and locally extensive in all cases and associated with the most frequently observed intralesional protozoans. Moderate to severe, multifocal, chronic to chronic-active, necrotizing myocarditis was also present in all cases. Additionally, less consistent inflammatory lesions occurred in the liver, lung and a mesenteric lymph node and were associated with fewer tachyzoites. Sera (n = 30) collected from free-ranging and captive Puerto Rican manatees and a rehabilitated/released Puerto Rican manatee from 2003 to 2012 were tested for antibodies for T. gondii. A positive T. gondii antibody titer was found in 2004 in 1 (3%) of the free-ranging cases tested. Disease caused by T. gondii is rare in manatees. This is the first report of toxoplasmosis in Antillean manatees from Puerto Rico. Additionally, these are the first reported cases of disseminated toxoplasmosis in any sirenian. The documentation of 4 cases of toxoplasmosis within one year and the extremely low seroprevalence to T. gondii suggest that toxoplasmosis may be an emerging disease in Antillean manatees from Puerto Rico.

Nonischemic left ventricular scar and cardiac sudden death in the young.

PubMed

di Gioia, Cira R T; Giordano, Carla; Cerbelli, Bruna; Pisano, Annalinda; Perli, Elena; De Dominicis, Enrico; Poscolieri, Barbara; Palmieri, Vincenzo; Ciallella, Costantino; Zeppilli, Paolo; d'Amati, Giulia

2016-12-01

Nonischemic left ventricular scar (NLVS) is a pattern of myocardial injury characterized by midventricular and/or subepicardial gadolinium hyperenhancement at cardiac magnetic resonance, in absence of significant coronary artery disease. We aimed to evaluate the prevalence of NLVS in juvenile sudden cardiac death and to ascertain its etiology at autopsy. We examined 281 consecutive cases of sudden death of subjects aged 1 to 35 years. NLVS was defined as a thin, gray rim of subepicardial and/or midmyocardial scar in the left ventricular free wall and/or the septum, in absence of significant stenosis of coronary arteries. NLVS was the most frequent finding (25%) in sudden deaths occurring during sports. Myocardial scar was localized most frequently within the left ventricular posterior wall and affected the subepicardial myocardium, often extending to the midventricular layer. On histology, it consisted of fibrous or fibroadipose tissue. Right ventricular involvement was always present. Patchy lymphocytic infiltrates were frequent. Genetic and molecular analyses clarified the etiology of NLVS in a subset of cases. Electrocardiographic (ECG) recordings were available in more than half of subjects. The most frequent abnormality was the presence of low QRS voltages (<0.5 mV) in limb leads. In serial ECG tracings, the decrease in QRS voltages appeared, in some way, progressive. NLVS is the most frequent morphologic substrate of juvenile cardiac sudden death in sports. It can be suspected based on ECG findings. Autopsy study and clinical screening of family members are required to differentiate between arrhythmogenic right ventricular cardiomyopathy/dysplasia and chronic acquired myocarditis. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytotoxic Escherichia coli strains encoding colibactin isolated from immunocompromised mice with urosepsis and meningitis

PubMed Central

Feng, Yan; Mannion, Anthony; Ge, Zhongming; Garcia, Alexis; Scott, Kathleen E.; Caron, Tyler J.; Jacobsen, Johanne T.; Victora, Gabriel; Jaenisch, Rudolf; Fox, James G.

2018-01-01

Immune-compromised mouse models allow for testing the preclinical efficacy of human cell transplantations and gene therapy strategies before moving forward to clinical trials. However, CRISPR/Cas9 gene editing of the Wsh/Wsh mouse strain to create an immune-compromised model lacking function of Rag2 and Il2rγ led to unexpected morbidity and mortality. This warranted an investigation to ascertain the cause and predisposing factors associated with the outbreak. Postmortem examination was performed on 15 moribund mice. The main lesions observed in these mice consisted of ascending urogenital tract infections, suppurative otitis media, pneumonia, myocarditis, and meningoencephalomyelitis. As Escherichia coli strains harboring polyketide synthase (pks) genomic island were recently isolated from laboratory mice, the tissue sections from the urogenital tract, heart, and middle ear were subjected to E. coli specific PNA-FISH assay that revealed discrete colonies of E. coli associated with the lesions. Microbiological examination and 16S rRNA sequencing confirmed E. coli-induced infection and septicemia in the affected mice. Further characterization by clb gene analysis and colibactin toxicity assays of the pks+ E. coli revealed colibactin-associated cytotoxicity. Rederivation of the transgenic mice using embryo transfer produced mice with an intestinal flora devoid of pks+ E. coli. Importantly, these barrier-maintained rederived mice have produced multiple litters without adverse health effects. This report is the first to describe acute morbidity and mortality associated with pks+ E. coli urosepsis and meningitis in immunocompromised mice, and highlights the importance of monitoring and exclusion of colibactin-producing pks+ E. coli. PMID:29554148

Successful treatment with tacrolimus in TAFRO syndrome: two case reports and literature review

PubMed Central

Shirai, Taiichiro; Onishi, Akira; Waki, Daisuke; Saegusa, Jun; Morinobu, Akio

2018-01-01

Abstract Rationale: TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome. Patient concerns: Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly. Diagnoses: In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients’ laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis. Interventions and outcomes: In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy. Lessons: This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome. PMID:29879072

Mechanical circulatory support in pediatrics

PubMed Central

De Rita, Fabrizio; Hasan, Asif; Griselli, Massimo

2014-01-01

There is no reliable published data on the overall prevalence or incidence of heart failure (HF) in children. However, the success of mechanical circulatory support (MCS) in management of HF has raised the prospect of a previously unavailable treatment modality. Orthotopic heart transplant (OHTx) remains the gold standard treatment, but the number of patients requiring this treatment far outweighs the donor availability. It is therefore not surprising to see the popularity of various MCS modalities, with different devices ranging from veno-arterial extra corporeal membrane oxygenation (VA-ECMO) to ventricular assist devices (VADs), which are either para-corporeal or intra-corporeal, with pulsatile or continuous flow. Indication, timing and the choice of the type of mechanical support are crucial so in order to avoid potential lethal complications such as hemorrhage, thrombo-embolism and infections. In the pediatric population, MCS is used mainly as bridge to transplantation but can be used as bridge to recovery in patients with acute myocarditis or following open-heart surgery. Active research is currently underway to develop newer and more durable devices that will assist the pediatric population across all age groups. This research will support different pathologies that have lower incidences of major morbidities, particularly as greater durations of MCS are expected due to a paucity of donors for OHTx. The combined experience developed through the usage of different devices in pediatric and adult populations has led to the to the application of MCS in some subgroups of grown–up congenital heart diseases (CHDs) patients, particularly those with systemic right ventricular failure. PMID:25452912

Left ventricular hypertrophy: The relationship between the electrocardiogram and cardiovascular magnetic resonance imaging.

PubMed

Bacharova, Ljuba; Ugander, Martin

2014-11-01

Conventional assessment of left ventricular hypertrophy (LVH) using the electrocardiogram (ECG), for example, by the Sokolow-Lyon, Romhilt-Estes or Cornell criteria, have relied on assessing changes in the amplitude and/or duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV mass have typically been validated by imaging with echocardiography or cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result of diverse etiologies, and LVH is also characterized by pathological changes in myocardial tissue characteristics on the genetic, molecular, cellular, and tissue level beyond a pure increase in the number of otherwise normal cardiomyocytes. For example, slowed conduction velocity through the myocardium, which can be due to diffuse myocardial fibrosis, has been shown to be an important determinant of conventional ECG LVH criteria regardless of LV mass. Myocardial tissue characterization by CMR has emerged to not only quantify LV mass, but also detect and quantify the extent and severity of focal or diffuse myocardial fibrosis, edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry disease), or iron (siderosis). This can be undertaken using CMR techniques including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2* mapping, extracellular volume fraction (ECV) mapping, fat/water-weighted imaging, and diffusion tensor CMR. This review presents an overview of current and emerging concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH. © 2014 Wiley Periodicals, Inc.

West Nile Virus Infection in Ruffed Grouse ( Bonasa umbellus): Experimental Infection and Protective Effects of Vaccination.

PubMed

Nemeth, Nicole M; Bosco-Lauth, Angela M; Williams, Lisa M; Bowen, Richard A; Brown, Justin D

2017-11-01

Ruffed grouse ( Bonasa umbellus) population numbers in Pennsylvania dramatically declined during the early 2000s and have subsequently remained depressed throughout much of the state. While this decline has been temporally associated with the presence of West Nile virus (WNV), lack of information on the WNV susceptibility of this popular game bird species has limited the ability to interpret the potential impacts of WNV. To address this knowledge gap, virologic, immunologic, pathologic, and clinical responses as well as protective effects of vaccination following experimental WNV inoculation in ruffed grouse were assessed. Four of 10 (40%) naive, WNV-inoculated grouse succumbed to infection within 8 days and had moderate mean peak viremia titers (10 7.0 plaque-forming units [PFU]/ml serum); severe necrotizing myocarditis with widespread, corresponding immunohistochemical labeling; and minimal encephalitis. Grouse that survived to the prescribed end point of 14 days postinoculation (6/10; 60%) had slightly lower mean peak viremia titers (10 6.8 PFU/ml serum), moderate myocardial lesions, and more widespread brain lesions with rare corresponding immunohistochemical labeling. Vaccinated, WNV-inoculated birds ( n = 5) had lower mean peak viremia titers (10 3.6 PFU/ml serum) and minimal lesions, and sham-inoculated, in-contact control birds ( n = 3) had no evidence of infection. All surviving, inoculated birds seroconverted, and WNV-specific antibodies were detectable in serum and Nobuto filter paper strip-eluted blood samples. These data suggest that WNV could serve as an additional population pressure on ruffed grouse in regions where transmission levels are high and WNV competent, ornithophilic vectors exist.